- THE PALLADIUM(II)-PROMOTED HYDROLYSIS OF METHYL AND ISOPROPYL GLYCYLGLYCINATE
-
The palladium(II)-promoted hydrolysis of methyl glycylglycinate and isopropyl glycylglycinate has been studied at four temperatures (25, 30, 35, and 40 deg C) at I=0.1 mol dm-3 in the pH range 4-5.Under these conditions, and at a 1:1 metal to ligand ratio, the peptide esters act as tridentate ligands, donation occuring via the terminal amino-group, the deprotonated amide nitrogen, and the carbonyl group of the ester.Rate constants are reported for hydrolysis of the ester function by water and hydroxide ion, and activation parameters calculated.Base hydrolysis of the co-ordinated peptide esters is ca. 1E5 times faster than the unproto nated peptide esters.Mechanisms for the reactions are considered.
- Hay, Robert W.,Pujari, Mahesh P.
-
-
Read Online
- Mechanochemical Prebiotic Peptide Bond Formation**
-
The presence of amino acids on the prebiotic Earth, either stemming from endogenous chemical routes or delivered by meteorites, is consensually accepted. Prebiotically plausible pathways to peptides from inactivated amino acids are still unclear as most oligomerization approaches rely on thermodynamically disfavored reactions in solution. Now, a combination of prebiotically plausible minerals and mechanochemical activation enables the oligomerization of glycine at ambient temperature in the absence of water. Raising the reaction temperature increases the degree of oligomerization concomitantly with the formation of a commonly unwanted cyclic glycine dimer (DKP). However, DKP is a productive intermediate in the mechanochemical oligomerization of glycine. The findings of this research show that mechanochemical peptide bond formation is a dynamic process that provides alternative routes towards oligopeptides and establishes new synthetic approaches for prebiotic chemistry.
- Cindro, Nikola,Grube?i?, Sa?a,Hernández, José G.,Me?trovi?, Ernest,Stolar, Tomislav,U?arevi?, Krunoslav
-
supporting information
p. 12727 - 12731
(2021/05/07)
-
- En Route to a Heterogeneous Catalytic Direct Peptide Bond Formation by Zr-Based Metal-Organic Framework Catalysts
-
Peptide bond formation is a challenging, environmentally and economically demanding transformation. Catalysis is key to circumvent current bottlenecks. To date, many homogeneous catalysts able to provide synthetically useful methods have been developed, while heterogeneous catalysts remain largely restricted to the studies addressing the prebiotic formation of peptides. Here, the catalytic activity of Zr6-based metal-organic frameworks (Zr-MOFs) toward peptide bond formation is investigated using dipeptide cyclization as a model reaction. Unlike previous catalysts, Zr-MOFs largely tolerate water, and reactions are carried out under ambient conditions. Notably, the catalyst is recyclable and no additives to activate the COOH group are necessary, which are common limitations of previous methods. In addition, a broad reaction scope tolerates substrates with bulky and Lewis basic groups. The reaction mechanism was assessed by detailed mechanistic and computational studies and features a Lewis acid activation of carboxylate groups by Zr centers toward amine addition in which an alkoxy ligand on adjacent Zr sites assists in lowering the barrier of key proton transfers. The proposed concepts were also used to study the formation of intermolecular peptide bond formation. While intrinsic challenges associated with the catalyst structure and water removal limit a more general intermolecular reaction scope under current conditions, the results suggest that further design of Zr-MOF catalysts could render these materials broadly useful as heterogeneous catalysts for this challenging transformation.
- Conic, Dragan,De Azambuja, Francisco,Harvey, Jeremy N.,Loosen, Alexandra,Parac-Vogt, Tatjana N.,Van Den Besselaar, Maxime
-
p. 7647 - 7658
(2021/06/30)
-
- Effect of high hydrostatic pressure on prebiotic peptide synthesis
-
Prebiotic peptide synthesis is a central issue concerning life's origins. Many studies considered that life might come from Hadean deep-sea environment, that is, under high hydrostatic pressure conditions. However, the properties of prebiotic peptide formation under high hydrostatic pressure conditions have seldom been mentioned. Here we report that the yields of dipeptides increase with raised pressures. Significantly, effect of pressure on the formation of dipeptide was obvious at relatively low temperature. Considering that the deep sea is of high hydrostatic pressure, the pressure may serve as one of the key factors in prebiotic peptide synthesis in the Hadean deep-sea environment. The high hydrostatic pressure should be considered as one of the significant factors in studying the origin of life.
- Ying, Jianxi,Chen, Peng,Wu, Yile,Yang, Xu,Yan, Kaili,Xu, Pengxiang,Zhao, Yufen
-
supporting information
p. 367 - 370
(2018/06/18)
-
- Synthesis of Deuterated or Tritiated Glycine and Its Methyl Ester
-
Abstract: Heating glycine (Gly) and methyl glycinate (GlyOCH3) supported on 5% Pd/C or 5% Pt/C in a deuterium or tritium gas atmosphere gave the isotope-labeled products. The experiments were carried out at 180°C for 10 min. The deuterium atom inclusion under these conditions averaged up to 1.8 atoms per molecule for Gly and up to 1.0 atom per molecule for GlyOCH3. The reaction with tritium gas gave labeled products with a specific radioactivity of 27–31 Ci/mmol for Gly and 18 Ci/mmol for GlyOCH3.
- Shevchenko,Andreeva,Nagaev, I. Yu.,Myasoedov
-
p. 266 - 267
(2019/01/03)
-
- Superactivity of MOF-808 toward Peptide Bond Hydrolysis
-
MOF-808, a Zr(IV)-based metal-organic framework, has been proven to be a very effective heterogeneous catalyst for the hydrolysis of the peptide bond in a wide range of peptides and in hen egg white lysozyme protein. The kinetic experiments with a series of Gly-X dipeptides with varying nature of amino acid side chain have shown that MOF-808 exhibits selectivity depending on the size and chemical nature of the X side chain. Dipeptides with smaller or hydrophilic residues were hydrolyzed faster than those with bulky and hydrophobic residues that lack electron rich functionalities which could engage in favorable intermolecular interactions with the btc linkers. Detailed kinetic studies performed by 1H NMR spectroscopy revealed that the rate of glycylglycine (Gly-Gly) hydrolysis at pD 7.4 and 60 °C was 2.69 × 10-4 s-1 (t1/2 = 0.72 h), which is more than 4 orders of magnitude faster compared to the uncatalyzed reaction. Importantly, MOF-808 can be recycled several times without significantly compromising the catalytic activity. A detailed quantum-chemical study combined with experimental data allowed to unravel the role of the {Zr6O8} core of MOF-808 in accelerating Gly-Gly hydrolysis. A mechanism for the hydrolysis of Gly-Gly by MOF-808 is proposed in which Gly-Gly binds to two Zr(IV) centers of the {Zr6O8} core via the oxygen atom of the amide group and the N-terminus. The activity of MOF-808 was also demonstrated toward the hydrolysis of hen egg white lysozyme, a protein consisting of 129 amino acids. Selective fragmentation of the protein was observed with 55% yield after 25 h under physiological pH.
- Ly, Hong Giang T.,Fu, Guangxia,Kondinski, Aleksandar,Bueken, Bart,De Vos, Dirk,Parac-Vogt, Tatjana N.
-
p. 6325 - 6335
(2018/05/14)
-
- Comparative study of the reactivity of zirconium(IV)-substituted polyoxometalates towards the hydrolysis of oligopeptides
-
The hydrolytic activity of the ZrIV-substituted Keggin-type (Et2NH2)8[{α-PW11O39Zr-(μ-OH)(H2O)}2]·7H2O (1), Lindqvist-type (Me4N)2[W5O18Zr(H2O)3] (2), and Wells-Dawson-type Na14[Zr4(P2W16O59)2(μ3-O)2(OH)2(H2O)4]·57H2O (3) polyoxometalates (POMs) towards the peptide bonds in the oligopeptides triglycine, tetraglycine, glycylglycylhistidine, and glycylserylphenylalanine was investigated by kinetic methods and multinuclear NMR spectroscopy. 31P NMR and UV/Vis spectroscopy showed that 1-3 were stable under the conditions used to study peptide bond hydrolysis. The reactivity of 1-3 towards oligopeptides was compared on the basis of the amount of free glycine produced at a certain time increment. In the presence of 1-3, rate constants in the range 6.25×10-7 to 10.14×10-7 s-1 were obtained, whereas no hydrolysis was observed after one month in the absence of these POMs. The results showed that the Keggin-type complex 1 was the most active towards peptide bond hydrolysis in tri- and tetrapeptides. 1H and 13C NMR spectroscopy showed that triglycine, tetraglycine, and glycylserylphenylalanine interact with 1 and 2 preferentially through the amine nitrogen atom and the N-terminal amide oxygen atom to activate the peptide bond towards hydrolysis. The coordination of glycylglycylhistidine resulted in multiple complexes with 1-3 as a result of additional imidazole coordination to the ZrIV centers.
- Ly, Hong Giang T.,Absillis, Gregory,Parac-Vogt, Tatjana N.
-
p. 2206 - 2215
(2015/05/13)
-
- Coupling-Reagent-Free Synthesis of Dipeptides and Tripeptides Using Amino Acid Ionic Liquids
-
A general method for the synthesis of dipeptides has been developed, which does not require any coupling reagents. This method is based on the reaction of readily available HCl salts of amino acid methyl esters with tetrabutylphosphonium amino acid ionic liquids. The isolation procedure of stepwise treatment with AcOH is easy to carry out. The method was extended to the synthesis of tripeptide, tyrosyl-glycyl-glycine, present in IMREG-1, also.
- Furukawa, Shinya,Fukuyama, Takahide,Matsui, Akihiro,Kuratsu, Mai,Nakaya, Ryotaro,Ineyama, Takashi,Ueda, Hiroshi,Ryu, Ilhyong
-
p. 11980 - 11983
(2015/08/18)
-
- Kilogram-Scale Synthesis of Osteogenic Growth Peptide (10-14) Using a Fragment Coupling Approach
-
Kilogram-scale synthesis of a bioactive pentapeptide in solution by "3 + 2" fragment coupling strategy has been successively accomplished in the development of OGP (10-14), a minimal OGP-derived sequence that retains the full proliferative activity of the osteogenic growth peptide. The synthetic scheme, coupling conditions, and scaling-up of the process are systematically studied; the epimerization of the tripeptide fragment and pentapeptide are also evaluated.
- Zhang, Teng,Chen, Zhenxing,Tian, Yan,Han, Bin,Zhang, Ning,Song, Wei,Liu, Zhulan,Zhao, Jinli,Liu, Jianli
-
supporting information
p. 1257 - 1262
(2015/09/28)
-
- Identification and characterization of prokaryotic dipeptidyl-peptidase 5 from porphyromonas gingivalis
-
Porphyromonas gingivalis, a Gram-negative asaccharolytic anaerobe, is a major causative organism of chronic periodontitis. Because the bacterium utilizes amino acids as energy and carbon sources and incorporates them mainly as dipeptides, a wide variety of dipeptide production processes mediated by dipeptidyl-peptidases (DPPs) should be beneficial for the organism. In the present study, we identified the fourth P. gingivalis enzyme, DPP5. In a dpp4-7-11-disrupted P. gingivalis ATCC 33277, a DPP7-like activity still remained. PGN-0756 possessed an activity indistinguishable from that of the mutant, and was identified as a bacterial orthologue of fungal DPP5, because of its substrate specificity and 28.5% amino acid sequence identity with an Aspergillus fumigatus entity. P. gingivalis DPP5 was composed of 684 amino acids with a molecular mass of 77,453, and existed as a dimer while migrating at 66 kDa on SDS-PAGE. It preferred Ala and hydrophobic residues, had no activity toward Pro at the P1 position, and no preference for hydrophobic P2 residues, showed an optimal pH of 6.7 in the presence of NaCl, demonstrated Km and kcat/Km values for Lys-Ala-MCA of 688 μM and 11.02 μM-1 s-1, respectively, and was localized in the periplasm. DPP5 elaborately complemented DPP7 in liberation of dipeptides with hydrophobic P1 residues. Examinations of DPP- and gingipain gene-disrupted mutants indicated that DPP4, DPP5, DPP7, and DPP11 together with Arg- and Lys-gingipains cooperatively liberate most dipeptides from nutrient oligopeptides. This is the first study to report that DPP5 is expressed not only in eukaryotes, but also widely distributed in bacteria and archaea.
- Ohara-Nemoto, Yuko,Rouf, Shakh M. A.,Naito, Mariko,Yanase, Amie,Tetsuo, Fumi,Ono, Toshio,Kobayakawa, Takeshi,Shimoyama, Yu,Kimura, Shigenobu,Nakayama, Koji,Saiki, Keitarou,Konishi, Kiyoshi,Nemoto, Takayuki K.
-
p. 5436 - 5448
(2014/03/21)
-
- Amide bond hydrolysis in peptides and cyclic peptides catalyzed by a dimeric Zr(iv)-substituted Keggin type polyoxometalate
-
Detailed kinetic studies on the hydrolysis of glycylserine (Gly-Ser) and glycylglycine (Gly-Gly) in the presence of the dimeric zirconium(iv)-substituted Keggin type polyoxometalate (Et2NH2)8[{α -PW11O39Zr(μ-OH)(H2O)}2] ·7H2O (1) were performed by a combination of 1H, 13C and 31P NMR spectroscopy. The observed rate constants for the hydrolysis of Gly-Ser and Gly-Gly at pD 5.4 and 60 °C were 63.3 × 10-7 s-1 and 4.44 × 10-7 s -1 respectively, representing a significant acceleration as compared to the uncatalyzed reactions. The pD dependence of the rate constant for both reactions exhibited a bell-shaped profile with the fastest hydrolysis observed in the pD range of 5.5-6.0. Interaction of 1 with Gly-Ser and Gly-Gly via their amine nitrogen and amide oxygen was proven by 13C NMR spectroscopy. The effective hydrolysis of Gly-Ser in the presence of 1 is most likely a combination of the polarization of the amide oxygen due to its binding to the Zr(iv) ion in 1 and the intramolecular attack of the Ser hydroxyl group on the amide carbonyl carbon. The effect of temperature, inhibitors, and ionic strength on the hydrolysis rate constant was also examined. The solution structure of 1 was investigated by means of 31P NMR spectroscopy, revealing that its stability is highly dependent on pH, concentration and temperature. A 2.0 mM solution of 1 was found to be fully stable under hydrolytic conditions (pD 5.4 and 60 °C) both in the presence and in the absence of the dipeptides. The Royal Society of Chemistry 2013.
- Ly, Hong Giang T.,Absillis, Gregory,Parac-Vogt, Tatjana N.
-
p. 10929 - 10938
(2013/09/12)
-
- Design, synthesis, insecticidal evaluation and molecular docking studies of cis-nitenpyram analogues bearing diglycine esters
-
Based on the strategies of receptor structure-guided neonicotinoid design, a series of novel cis-nitenpyram analogues bearing diglycine esters were designed and synthesized. Preliminary bioassays indicated that the insecticidal spectra of the target compounds were expanded compared with our previous work, while all the target compounds presented excellent insecticidal activities against Nilaparvata lugens and Aphis medicagini at 100 mg/L. Among these analogues, 6b showed 100% mortality against Nilaparvata lugens (LC50 = 0.163 mg/L) and 90% against Aphis medicagini at 4 mg/L. SARs suggested that the insecticidal potency of our designed cis-nitenpyram analogues was dual-controlled by the size and species of the ester groups. The molecular docking simulations revealed that the structural uniqueness of these analogues may lead to a unique molecular recognition and binding mode compared with the previously designed compounds. Introduction of the peptide bond gave rise to more significant hydrogen bonds between the nitenpyram analogues bonding with the amino acid residues of insect nAChRs. The docking results explained the SARs observed in vitro, and shed light on the novel insecticidal mechanism of these cis-nitenpyram analogues.
- Chen, Yanxia,Sun, Chuanwen,Wen, Xiaxia,Zhang, Wanggeng
-
p. 159 - 168
(2013/07/26)
-
- Oligomerization of glycine and alanine on metal(II) octacynaomolybdate(IV): Role of double metal cyanides in prebiotic chemistry
-
Condensation reactions of amino acid (glycine and alanine) on the surface of metal(II) octacyanomolybdate( IV) (MOCMo) complexes are investigated using highperformance liquid chromatography (HPLC) and electron spray ionizations-mass spectroscopy (ESI-MS). The series of MOCMo have been synthesized and the effect of outer sphere metal ions present in the MOCMo on the oligomerization of glycine and alanine at different temperature and time found out. Formation of peptides was observed to start after 7 days at 60°C. Maximum yield of peptides was found after 35 days at 90°C. It has been found that zinc(II) octacyanomolybdate( IV) and cobalt(II) were the most effective metal cations present in outer sphere of the MOCMo for the production of high yield of oligomerized products. Surface area of MOCMo seems to play dominating parameter for the oligomerization of alanine and glycine. The results of the present study reveal the role of MOCMo in chemical evolution for the oligomerization of biomolecules. Springer-Verlag 2012.
- Kumar, Anand,Kamaluddin
-
p. 2417 - 2429
(2013/03/28)
-
- Efficient N-terminal labeling of proteins by use of sortase
-
"Sorting out" N-terminal labeling: The reversibility of transpeptidase reactions makes protein N-terminal labeling challenging. Depsipeptide substrates for sortase A release alcohol by-products, which are poor nucleophiles for the reverse reaction, during ligation. Proteins with an unhindered N-terminal glycine residue can be labeled efficiently with only a minimal excess of the labeling reagent (see scheme).
- Williamson, Daniel J.,Fascione, Martin A.,Webb, Michael E.,Turnbull, W. Bruce
-
supporting information
p. 9377 - 9380
(2012/11/06)
-
- Microbial enantioselective removal of the N-benzyloxycarbonyl amino protecting group
-
In order to deprotect N-carbobenzoxy-l-aminoacids (Cbz-AA) and related compounds, a series of microorganisms was selected from soil by enrichment cultures with Cbz-l-Glu as sole nitrogen source. A lyophilized whole-cell preparation of two Arthrobacter sp. strains grown on Cbz-Glu or Cbz-Gly exhibited a high cleavage activity. The conditions of hydrolysis have been optimized and a quantitative enantioselective deprotection of several Cbz-dl-amino acids was obtained, as well as the deprotection of N-carbamoylester derivatives of several synthetic amino compounds. The preparation of Cbz-d-allylglycine and l-allylglycine in high yield and high optical purity is described as an application of this method.
- Maurs, Michele,Acher, Francine,Azerad, Robert
-
-
- Peptide bond hydrolysis catalyzed by the Wells-Dawson Zr(α 2-P2W17O61)2 polyoxometalate
-
In this paper we report the first example of peptide hydrolysis catalyzed by a polyoxometalate complex. A series of metal-substituted Wells-Dawson polyoxometalates were synthesized, and their hydrolytic activity toward the peptide bond in glycylglycine (GG) was examined. Among these, the Zr(IV)- and Hf(IV)-substituted ones were the most reactive. Detailed kinetic studies were performed with the Zr(IV)-substituted Wells-Dawson type polyoxometalate K 15H[Zr(α2-P2W17O 61)2]·25H2O which was shown to act as a catalyst for the hydrolysis of the peptide bond in GG. The speciation of K 15H[Zr(α2-P2W17O 61)2]·25H2O which is highly dependent on the pD, concentration, and temperature of the solution, was fully determined with the help of 31P NMR spectroscopy and its influence on the GG hydrolysis rate was examined. The highest reaction rate (kobs = 9.2 (±0.2) × 10-5 min-1) was observed at pD 5.0 and 60 °C. A 10-fold excess of GG was hydrolyzed in the presence of K 15H[Zr(α2-P2W17O 61)2]·25H2O proving the principles of catalysis. 13C NMR data suggested the coordination of GG to the Zr(IV) center in K15H[Zr(α2-P2W 17O61)2]·25H2O via its N-terminal amine group and amide carbonyl oxygen. These findings were confirmed by the inactivity of K15H[Zr(α2-P2W 17O61)2]·25H2O toward the N-blocked analogue acetamidoglycylglycinate and the inhibitory effect of oxalic, malic, and citric acid. Triglycine, tetraglycine, and pentaglycine were also fully hydrolyzed in the presence of K15H[Zr(α2- P2W17O61)2]·25H2O yielding glycine as the final product of hydrolysis. K15H[Zr(α 2-P2W17O61)2] ·25H2O also exhibited hydrolytic activity toward a series of other dipeptides.
- Absillis, Gregory,Parac-Vogt, Tatjana N.
-
p. 9902 - 9910,9
(2012/12/11)
-
- Intermolecular phosphoryl transfer of N-phosphoryl amino acids
-
N-Phosphoryl amino acids (NPAAs) are a novel series of N-terminal-activated amino acids that act as the energy source and phosphoryl donor in intra- and intermolecular phosphoryl transfer to form "high-energy" species, such as acetyl phosphate and aminoacyl phosphates, and in the self-assembled synthesis of polypeptides under mild aqueous conditions. In this work, the chemical reactivity of N-mono(methoxyphosphoryl)glycine as a representative was investigated in detail by using a combination of the stable-isotope-labeling (15N) technique, 31P NMR, ESI-MS/MS and LC-MS. The phosphoryl group of NPAAs can be transferred intermolecularly to the carboxy group of another molecule through intramolecular cyclic pentacoordinate phosphoric-amino acid anhydride intermediates. In addition to C-terminal activation by phosphate anhydride, amino acids can also be self-activated by N-phosphorylation. This information not only provides some interesting clues for understanding the active role of the phosphoryl group in living systems, but also shows that the origin of life might be attributed to the chemical evolution of N-phosphoryl amino acids. Copyright
- Gao, Xiang,Deng, Honggui,Tang, Guo,Liu, Yan,Xu, Pengxiang,Zhao, Yufen
-
experimental part
p. 3220 - 3228
(2011/07/08)
-
- Molecular cloning and characterization of γ-Glutamyltranspeptidase from pseudomonas nitroreducens IFO12694
-
y-Glutamyltranspeptidase from Pseudomonas nitroreducens IFO12694 (PnGGT) exhibited higher hydro-lytic activity than transfer activity, as compared with other y-glutamyltranspeptidases (GGTs). PnGGT showed little activity towards most of L-amino acids and towards glycyl-glycine, which is often used as a standard y-glutamyl accepter in GGT transfer reactions. The preferred substrates for PnGGT as a y-glutamyl accepter were amines such as methylamine, ethylamine, and isopropylamine.
- Imaoka, Masashi,Yano, Shigekazu,Okumura, Masashi,Hibi, Takao,Wakayama, Mamoru
-
experimental part
p. 1936 - 1939
(2011/06/11)
-
- The peptide formation mediated by cyanate revisited. N-carboxyanhydrides as accessible intermediates in the decomposition of N-carbamoylamino acids
-
Similar to many ureas, N-carbamoylamino acids were shown to be hydrolyzed in aqueous solution through elimination mechanisms at close to neutral pH, the nucleophilic attack of water being a minor process. Two competing elimination mechanisms can take place involving either cyanate or isocyanate transient intermediates. Peptide formation was observed and attributed to the latter pathway through the intermediacy of amino acid N-carboxyanhydride (NCA). Eventually, cyanate and its precursors (including urea) unexpectedly behave as amino acid activating agents because of their ability in amino acid carbamoylation. Owing to its ability to generate a background prebiotic production of NCAs on the primitive Earth, this reaction is suggested to have contributed to the origin of life process. Copyright
- Danger, Gregoire,Boiteau, Laurent,Cottet, Herve,Pascal, Robert
-
p. 7412 - 7413
(2007/10/05)
-
- Threonine transformation under hydrothermal conditions
-
In order to revisit the kinetics of amino acid transformation in the chemical evolution, a series of hydrothermal experiments has been conducted for threonine (Thr) solution. Thr transformed into glycine (Gly) and other products including peptides and polymers at 121 to 160°C. The Thr → Gly decomposition rate (k1 ) is different from apparent Thr decreasing rate (k), because of the presence of other side reactions. Copyright
- Shiota, Dai,Nakashima, Satoru
-
p. 158 - 159
(2007/10/03)
-
- A reaction network for triglycine synthesis under hydrothermal conditions
-
It has been hypothesized that chemical evolution leading to the origin of life might have occurred in hydrothermal environments on primitive Earth. To examine this hypothesis, we investigated how the polymerization of amino acids proceeds under high-temperature and high-pressure conditions. We investigated a reaction network consisting of glycine and oligoglycines up to trimer, and the condensation/hydrolysis reactions among these molecules. We determined the rate constants of these reactions in experiments employing a flow reactor at 200 °C and 25 MPa. We found that two condensation reactions of glycine, which yield diglycine and diketopiperazine as products, have larger equilibrium constants under these conditions than at 25 °C. This result supports the hypothesis that hydrothermal conditions are thermodynamically favorable for chemical evolution. We also found that triglycine formation is mediated by diketopiperazine at 200 °C and 25 MPa. This implies that diketopiperazine acts as an important intermediate in the polymerization process of amino acids, which might have occurred in hydrothermal environments on primitive Earth.
- Mitsuzawa, Shigenobu,Yukawa, Tetsuyuki
-
p. 965 - 973
(2007/10/03)
-
- Reaction of amino acids in a supercritical water-flow reactor simulating submarine hydrothermal systems
-
A novel supercritical water flow-reactor was constructed in order to simulate submarine hydrothermal systems. The temperature of fluid inside the reaction tube could be monitored with thermocouples, which was proved to be different from the temperature outside the reaction tube. Oligomers of glycine up to tetraglycine were formed when a 100 mM glycine solution was heated at 200-350 °C for 2 minutes. None of glycine peptides were produced at 400 °C. It was suggested, however, that the formation of glycine condensates at higher temperature, including supercritical conditions of water. The stability of some amino acids under hydrothermal conditions was examined. ω-Amino acids and glutamic acid, which can form intramolecular condensates, showed higher stability than other α-amino acids at higher temperature, including supercritical conditions.
- Islam, Md. Nazrul,Kaneko, Takeo,Kobayashi, Kensei
-
p. 1171 - 1178
(2007/10/03)
-
- Metal-catalyzed hydroxylaminolysis of unactivated amide and peptide bonds.
-
Kinetics of the hydroxylaminolysis of acetamide, glycinamide, glycylglycine and triglycine have been studied in the range of temperatures 37-60 degrees C as a function of pH and hydroxylamine concentration. Rate constants for specific acid, general-acid and general-base catalyzed pathways have been determined for all substrates (for glycine derivatives rate constants for different protonation forms were obtained). Testing different metal ions as possible reaction catalysts revealed a significant catalytic effect of Zn(II) on the hydroxylaminolysis of glycine substrates, but not acetamide. On the basis of the kinetic results, a mechanism of Zn(II) catalysis is proposed, which involves the coordination of the metal ion to the alpha-amino group of the substrate and the base-assisted nucleophilic attack of hydroxylamine on the bound substrate. The product analysis by proton NMR shows that the primary reaction product in the catalytic reaction is glycine hydroxamic acid, which undergoes further Zn(II)-catalyzed hydrolysis to glycine. Thus the final result of the Zn(II)-catalyzed treatment of peptides by hydroxylamine is hydrolytic cleavage.
- Gomez-Reyes, Baldomero,Yatsimirsky, Anatoly K
-
p. 866 - 872
(2007/10/03)
-
- Enantioselective Enzymatic Cleavage of N-Benzyloxycarbonyl Groups
-
A new enzymatic process for the enantioselective cleavage of N-benzyloxycarbonyl (Cbz) groups from protected amino acids and related compounds has been developed. The Cbz-deprotecting enzyme was isolated from cell extracts of Sphingomonas paucimobilis SC 16113 and purified to homogeneity. The purified protein has a molecular weight of 155,000 daltons and a subunit size of 44,000 daltons.
- Patel, Ramesh N.,Nanduri, Venkata,Brzozowski, David,McNamee, Clyde,Banerjee, Amit
-
p. 830 - 834
(2007/10/03)
-
- Spectroscopy of hydrothermal reactions. 27. Simultaneous determination of hydrolysis rate constants of glycylglycine to glycine and glycylglycine-diketopiperazine equilibrium constants at 310-330°C and 275 bar
-
Hydrolysis rate constants of glycylglycine to glycine and equilibrium constants between glycylglycine and diketopiperazine were determined simultaneously in situ using an FT-IR spectroscopy flow reactor at 310-330°C and 275 bar. The hydrolysis of the peptide bond in neutral hydrothermal solution follows the first-order (or pseudo-first-order) rate law. The cyclization of dipeptides is very prominent at high temperatures. Pressure affects the hydrolysis rate and the enthalpy of cyclization of the dipeptide. Specifically, the activation energy for hydrolysis of the dipeptide is reduced by about 50 kJ/mol and the standard enthalpy change of cyclization of the dipeptide is increased by about 50 kJ/mol when pressure is increased from a stream pressure of 1-16 bar to a solution pressure of 275 bar. The data analysis method used in this work is general and could be applied to other dipeptides provided the decomposition rate of the free amino acid product of hydrolysis is monitored.
- Li, Jun,Brill, Thomas B.
-
p. 8575 - 8577
(2007/10/03)
-
- Selective formation of glycylglycine by dehydration of glycine adsorbed on silica gel
-
Silica gel promotes the selective dehydration of glycine to form intermediate glycylglycine, with inhibition of the formation of stable glycine anhydride and polymer products. IR measurements indicate that glycine adsorbed on silica gel results in the formation of neutral species having C=O and NH2 groups. The species is considered to stimulate dehydration, leading to the reported selective dehydration. Copyright
- Ogawa, Haruo,Fujigaki, Tamiki,Chihara, Teiji
-
p. 354 - 356
(2007/10/03)
-
- Rates of reduction of N-chlorinated peptides by sulfite: Relevance to incomplete dechlorination of wastewaters
-
Biologically induced fragmentation of proteins during wastewater treatment produces peptides, which form long-lasting organic chloramines when the water is disinfected with Cl2. To protect aquatic wildlife from residual chlorine, including chloramines, wastewaters are often treated with sulfur dioxide or sulfite salts. This strategy incompletely eliminates residual chlorine species. Here we report that dechlorination rate constants of N- chloropeptides are 1-2 orders of magnitude smaller than those for NH2Cl and some aliphatic organic chloramines. Slow rates explain the prevalence of N- chloropeptides in dechlorinated wastewaters after faster reacting chlorine species have been eliminated. Dechlorination is subject to general acid catalysis. For N-chlorinated leucylalanine, the rate law above pH 6 in phosphate buffer at 25 °C and / ? 0.1 M is as follows: rate = (9.92 ± 0.41 x 103[H2PO4-] + 5.70 ± 0.52 x 108[H3O+] + 5.3 ± 0.2)[SO32-][Cl- Leu-Ala] (concentrations in M, time in s). Rate constants for other peptides appear to be of similar magnitude; variations in the acid-catalyzed terms among different hydrophobic peptides correlate with solvation energies of side chains. The kinetic data suggest that reducing N-chloropeptides in wastewaters by 75% or more will require reaction times generally >0.5 h at environmentally acceptable S(IV) doses and pH values. Biologically induced fragmentation of proteins during wastewater treatment produces peptides, which form long-lasting organic chloramines when the water is disinfected with Cl2. To protect aquatic wildlife from residual chlorine, including chloramines, wastewaters are often treated with sulfur dioxide or sulfite salts. This strategy incompletely eliminates residual chlorine species. Here we report that dechlorination rate constants of N-chloropeptides are 1-2 orders of magnitude smaller than those for NH2Cl and some aliphatic organic chloramines. Slow rates explain the prevalence of N-chloropeptides in dechlorinated wastewaters after faster reacting chlorine species have been eliminated. Dechlorination is subject to general acid catalysis. For N-chlorinated leucylalanine, the rate law above pH 6 in phosphate buffer at 25 °C and I≈0.1 M is as follows: rate = (9.92±0.41×103[H2 PO4- ]+5.70±0.52×108[ H3O+]+5.3±0.2) [SO32-][Cl-Leu-Ala] (concentrations in M, time in s). Rate constants for other peptides appear to be of similar magnitude; variations in the acid-catalyzed terms among different hydrophobic peptides correlate with solvation energies of side chains. The kinetic data suggest that reducing N-chloropeptides in wastewaters by 75% or more will require reaction times generally >0.5 h at environmentally acceptable SIV doses and pH values.
- Jensen, James S.,Helz, George R.
-
p. 516 - 522
(2007/10/03)
-
- New carriers for representative peptides and peptide drugs
-
3,5-Disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives; 4a-g were prepared and found to be a promising prodrug approach for peptide drugs. The pH profile for their degradation in aqueous buffer solutions was determined using HPLC technique and accounted for, in terms of specific base-catalyzed reactions. All of the compounds however, showed high acid-stability. Enzymatic (human serum) hydrolysis of the different derivatives offered an advantageous range of t( 1/4 )'s, the property that permits controlling onset and duration of actions of drugs.
- Aboul-Fadl, Tarek,El-Shorbagi, Abdel-Nasser
-
p. 327 - 332
(2007/10/03)
-
- Reaction enthalpies for M+L = M+ + L, where M+ = Na+ and K+ and L = acetamide, N-methylacetamide, N,N-dimethylacetamide, glycine, and glycylglycine, from determinations of the collision-induced dissociation thresholds
-
With electrospray (ES), ions present in solution can be transferred to the gas phase. The method provides unique opportunities for studies of hitherto inaccessible ions. Collision-induced dissociation threshold measurements of gas phase ions produced by ES are described. The thresholds for the reactions M+L = M+ + L, where M+ is Na+ or K+ and L is acetone, dimethyl sulfoxide, acetamide, N-methylacetamide, N,N-dimethylacetamide, glycine, glycinamide, succinamide, and glycylglycine, were determined. Enthalpy changes for the reaction were derived from these data.
- Klassen, John S.,Anderson, Stephen G.,Blades, Arthur T.,Kebarle, Paul
-
p. 14218 - 14227
(2007/10/03)
-
- Influence of Alkali- and Alkaline-earth-metal Cations on the 'Salt-induced Peptide Formation' Reaction
-
The reaction mechanism of the salt-induced peptide formation from amino acids has been investigated by variation of the inorganic salt delivering Cl(1-) ions and providing the dehydrating effect.Chloride anions proved to be essential to prevent chelate complexation of the second amino acid.Upon exchange of sodium by other alkali- or alkaline-earth elements, peptide formation is still observed.The dipeptide yields are mainly determined by two factors: on the one hand the pH of the solution should be below 3 to prevent Cu(II)-catalysed peptide hydrolysis and give an optimum species distribution for peptide formation and above 2 to keep proton-catalysed peptide hydrolysis as low as possible; on the other hand by the concentration of the inorganic salt for removing water from the reaction and thus shifting the equilibrium towards the peptide side.The hydration enthalpies of the cations are the determining factor for the initial rate of peptide formation and lead to the series Mg(2+) > Ca(2+) > Ba(2+) > Na(1+) > NH4(1+) > K(1+) > Cs(1+).In the long run the initial advantage of divalent cations is overruled by stronger hydrolysis due to the lower pH of their solutions.The ion NH4(1+) is atypical, apparently due to its buffering ability.
- Eder, Artur H.,Rode, Bernd M.
-
p. 1125 - 1130
(2007/10/02)
-
- On the Possible Role of Montmorillonites in Prebiotic Peptide Formation
-
The ability of montmorillonite clay minerals for catalyzing peptide formation from amino acids in aqueous solution has been investigated using glycine and Cu(2+) and Ca(2+) containing montmorillonites as reaction systems.Evaporation cycle experiments showed that minor amounts of di- and tripeptide are formed from the amino acid.Further polymerization of dipeptide, however, seems to be more favoured by this reaction system than the initial step of dipeptide formation, and a possible role of clays in prebiotic peptide evolution could be seen therefore in the prolongation of peptide chains.Cu(2+) ions in the clay matrix did not show any advantage over the usual Ca(2+) ions embedded in natural montmorillonite. - Keywords: Prebiotic peptide formation; Evolution; Clay catalysis.
- Bujdak, J.,Slosiarikova, H.,Texler, N.,Schwendinger, M.,Rode, B. M.
-
p. 1033 - 1040
(2007/10/02)
-
- Chromatographic method for the determination of conditional equilibrium constants for the carbamate formation reaction from amino acids and peptides in aqueous solution
-
A novel and sensitive method has been developed and evaluated for the study of carbamate formation equilibria of amino acids and peptides in aqueous solution. The method is based on reversed-phase liquid chromatography with cetyltrimethylammonium bromide. The reliability of the method was established by comparing the results determined from the present study with the few data in the literature. The relaxation rate of the carbamate reaction was shown to be faster than the chromatographic distribution relaxation rate (seconds). As a result, the retention time of amine solutes is increased in the presence of CO2. Carbamate formation constants and mole fractions of carbamates at physiological pH of eleven L-α-amino acids and peptides were determined. No correlation between the formation constant and the ammonium pKa was found. There is significant dependence of the amount of a particular amino acid or peptide that exists as carbamate at pH 7.4 on the pKa of the ammonium group, however. This is due to mass action rather than reflecting the influence of pKa on the propensity of the amine to react with CO2. It is suggested that amino acids and peptides with ammonium pKa greater than 9.5 do not form significant amounts of carbamates in aqueous solution near neutral pH.
- Chen, Jian-Ge,Sandberg, Mats,Weber, Stephen G.
-
p. 7343 - 7350
(2007/10/02)
-
- SYNTHESIS OF DIPEPTIDE ESTERS OF METRONIDAZOLE AND EVALUATION OF THEIR HYDROLYTIC STABILITY
-
Amino acid and dipeptide esters of metronidazole were synthesized and evaluated on their hydrolytic stability in various buffers and culture media.The hydrolytic susceptibility of the different esters was minimal in the pH range 3-5.In the alkaline region, pH 6.5-8, the half-lifes were of the order of 1-6.6 hrs.At alkaline pH the dipeptide esters were more susceptible towards hydrolysis.At pH 8.8 the observed half-life for the gly-gly and the gly-phe esters was 0.2 h, whereas for the gly and the phe ester it was 1.1 h, respectively 2.7 h.It was demonstrated that the increased rate of hydrolysis for the dipeptide esters was due to an intramolecular aminolysis with the formation of a diketopiperazine accompanied by the release of free metronidazole.
- Permentier, Dirk,Vansteenkiste, Stefan,Schacht, Etienne,Vermeersch, Hans,Remon, Jean Paul
-
p. 701 - 708
(2007/10/02)
-
- The Relationship between Taste and Primary Structure of "Delicious Peptide" (Lys-Gly-Asp-Glu-Glu-Ser-Leu-Ala) from Beef Soup
-
"Delicious peptide" was reported to be as delicious as beef soup.The peptide and its fragments were synthesized to study its taste active sites. "Delicious peptide" was found to produce a umami and a sour taste.By preparing several di- or tripeptides composed of basic or acidic amino acids, we found that the taste of "delicious peptide" was produced by an interaction between the basic and the acidic fragments in the peptide.
- Tamura, Masahiro,Nakatsuka, Tohru,Tada, Makoto,Kawasaki, Yoshihiro,Kikuchi, Eiichi,Okai, Hideo
-
p. 319 - 326
(2007/10/02)
-
- Direct Cleavage versus Transpeptidation in the Autodecomposition of Peptides Containing 2,4-Diaminobutanoic Acid (DABA) and 2,3-Diaminopropanoic Acid (DAPA) Residues. Specific Cleavage of DAPA-Containing Peptides
-
Peptides containing 2,4-diaminobutanoic acid and 2,3-diaminopropanoic acid residues undergo transpeptidation by attack of their side-chain amino groups on the N-carbonyl (eq. 2).Little or no direct cleavage by attack on the C-carbonyl (eq. 1) is observed.The transpeptidation reactions of peptides containing 2,4-diaminobutanoic acid (DABA) or 2,3-diaminopropanoic acid (DAPA) residues reach an equilibrium in which the various peptides studied are about 70-80percent transpeptidized; this extent of transpeptidation is in aggreement with the equilibrium constants for othertransamination reactions.The transpeptidation reaction is strongly catalyzed by phosphate and bicarbonate buffers, and the pH dependence of the reaction suggests that an unprotonated side-chain amino group is required for significant reactivity.The rate of the transpeptidation reaction is retarded by bulky substituents at the α-carbon of the residue at the amino-terminal side of the DAPA or DABA residue.The preference for transpeptidationdirect cleavage in the case of DABA residues can be explained by one or more of the following factors: (1) a preference for (Z)-amide (transpeptidation)(E)-amide (direct cleavage); (2) greater ring strain in the tetrahedral intermediate for direct cleavage; (3) a steric effect resulting from unfavorable interactions in the possible transition states for direct cleavage (Scheme III).A stereoelectronic explanation is considered and rejected.Peptides containing transpeptidized DABA and DAPA residues (isoDABA and isoDAPA residues, respectively) undergo cleavage at the carboxy-terminal side of these residues on treatment with the Edman reagent followed by treatment with trifluoroaceticacid.Peptides can be induced to undergo direct cleavage at the carboxy-terminal side of untranspeptidized DAPA residues by treatment with the Edman reagent followed by heptafluorobutyric acid.The chemical and biological significance of these observations is discussed.
- Blodgett, James K.,Loudon, G. Marc
-
p. 6813 - 6821
(2007/10/02)
-
- ATRIOPEPTINS. II. SYNTHESIS OF N-TERMINAL FRAGMENTS
-
Peptides, corresponding to the N-terminal sequence in atriopeptins, were synthesized by classical methods of peptide chemistry in solutions.The obtained peptides were characterized by various physicochemical methods.The scheme and methods of the synthesis are discussed.
- Ovchinnikov, Mikhail V.,Bespalova, Zhanna D.,Molokoedov, Aleksandr S.,Revenko, Inna V.,Sepetov, Nikolai F.,et al
-
p. 784 - 795
(2007/10/02)
-
- Pharmaceutical preparations having diuretic activity
-
Pharmaceutical preparations having diuretic activity and comprising a peptide of the formula STR1 wherein (a) R1 and R2 are hydrogen and R3 is --OH, or STR2 or Y, or wherein (b) R1 is hydrogen, R2 is CH2 OH or STR3 and R3 is --OH or Y, or wherein (c) R1 is --CH2 OH and R2 is hydrogen or STR4 and R3 is --OH or Y, or wherein (d) R1 is STR5 R2 is hydrogen or --CH2 OH and R3 is --OH, --NHCH2 COOH, or Y, and wherein X is hydrogen, methyl, prolyl, or an N-protective group, and Y is --NH2, --OR4, wherein R4 is linear or branched alkyl or cyclolalkyl having from 1 to 8 carbon atoms, benzyl, phenyl, or STR6
- -
-
-
- Peptide Synthesis Using the Pyrrole Ring as an Amino Protecting Group
-
The utility of a pyrrole ring as an amino protecting group for amino acids in peptide synthesis has been studied.The N-termini of various amino acids (1) were protected with a pyrrole ring by treatment with 2,5-dimethoxytetrahydrofuran (10) to give 2-substituted 2-(1-pyrrolyl)acetic acids (11).The peptide bond between (11) and amino acid methyl ester (2) was formed using N,N'-dicyclohexylcarbodiimide, and the pyrrole ring was cleaved by ozonolysis and hydrolysis without the cleavage of a peptide bond to give the corresponding dipeptide compounds (26) in good yields.
- Kashima, Choji,Maruyama, Tatsuya,Harada, Kazuo,Hibi, Shigeki,Omote, Yoshimori
-
p. 601 - 645
(2007/10/02)
-
- 4H-3,1-BENZOXAZIN-4-ONES AND RELATED COMPOUNDS AND USE AS ENZYME INHIBITORS
-
Novel 2-amino-4H-3,1-benzoxazin-4-ones represented by the formula wherein R 1, R 2, R 3 and X are defined herein are useful as enzyme inhibitors in animals.
- -
-
-
- PEPTIDE FORMATION FROM AMINO ACID WITH PARTICULATE SEMICONDUCTOR PHOTOCATALYSTS
-
Peptides of diglycine to pentaglycine are formed from glycine under irradiation in the presence of particulate semiconductor photocatalysts such as TiO2, CdS, CdSe, MoS2, In2O3, and GaP, with and without Pt deposition.Platinization of the semiconductors efficiently enhanced the yield of the peptides.
- Onoe, Jun,Kawai, Tomoji,Kawai, Shichio
-
p. 1667 - 1670
(2007/10/02)
-
- Reaction of Trimetaphosphate with Glycine
-
The reaction of trimetaphosphate (P3m) with glycine in an aqueous solution was studied. 1) P3m reacted with glycine at pH 10 and above to form two unknown compounds, A and B. 2) The amounts of these compounds were strongly affected by reaction conditions, such as the mixing ratio of P3m and glycine and the pH, and the yields of compounds A and B were around 26 and 24 percent, respectively. 3) Compound A was proved to be an orthophosphate derivative of glycine (P1-derivative of glycine), aminoacetyl phosphate, , while compound B was found to be a P1-derivative of glycine, N-(carboxymethyl)phosphoramidate, . 4) It was found that glycilglycine (dimer), glycilglycilglycine (trimer), and higher oligopeptides of glycine were formed in the reaction of P3m and glycine.Further, in the reaction at pH 10-14, tetra- (P4) and pentaphosphate (P5) were also formed besides compounds A and B, though in small quantities. 5) Short-chain phosphates, such as ortho-(P1), pyro-(P2) and triphosphate (P3), did not react with glycine at all. 6) The mechanism of the reaction of P3m with glycine is discussed.KEYWORDS-trimetaphosphate; glycine; aminoacetylphosphate; N-(carboxymethyl)phosphoroamidate; phosphorylation
- Tsuhako, Mitsumoto,Ohashi, Shigeru,Nariai, Hiroyuki,Motooka, Itaru
-
p. 3882 - 3889
(2007/10/02)
-
- 3,5-DINITRO-1-(p-NITROPHENYL)-4-PYRIDONE AS A NOVEL PROTECTIVE GROUP OF PRIMARY AMINES
-
3,5-Dinitro-1-(p-nitrophenyl)-4-pyridone is proposed as a novel protective group for primary amines, especially amino acids, based on the results of the transformation of 1-substituated 3,5-dinitro-4-pyridones with primary amines.
- Matsumura, Eizo,Ariga, Masahiro,Tohda, Yasuo,Kawashima, Toshihide
-
p. 757 - 758
(2007/10/02)
-
- SYNTHESIS, PROPERTIES, AND REACTIONS OF α- AND β-D-GLUCOPYRANOSYL ESTERS OF SOME TRIPEPTIDES
-
The 2,3,4,6-tetra-O-benzyl-1-O-(N-benzyloxycarbonyltripeptidyl)-D-glucopyranoses 1, 8, and 13 were synthesised from 2,3,4,6-tetra-O-benzyl-α-D-glucopyranose and the active esters of the appropriate N-protected tripeptides (Gly-Gly-Gly-, L-Phe-Gly-Gly-, and Gly-Gly-L-Phe-) in the presence of imidazole; the anomeric mixtures were resolved and the α and β anomers characterised.The β anomer of 13, containing the L and D enantiomers (ratio ca. 3:1) of Gly-Gly-Phe- as the aglycon, could be resolved by column chromatography into the pure isomeric forms.Catalytic hydrogenolysis of the β anomers, in the presence and absence of a strong acid, yielded the free 1-esters 2β, 9β, and 14β, which were characterised as the mono-oxalate or trifluoroacetate salts and as free bases.Similarly, the α anomers afforded 2α, 9α, and 14α, whereas omission of the strong acid led to accompanying 1 --> 2 acyl migration, to give the 2-O-acyl derivatives.All of the compounds prepared were converted into the N-acetyl and/or peracetylated derivatives.The 1-esters 2β and 9β, both in the charged and uncharged form, and the trifluoroacetate salt of 14β, are susceptible to cleavage by β-D-glucosidase; the enzyme had no effect on the uncharged form of 14β.This difference between 14β and its salt is discussed in conformational terms.
- Valentekovic, Stefica,Keglevic, Dina
-
-
- PREPARATIVE ISOLATION AND PROPERTIES OF DIASTEREOMERIC COPPER(II) CHELATES OF SCHIFF BASES OF DIPEPTIDES WITH (α-(N,N-DIMETHYLAMINO)ALKYL)FORMYLCYMANTRENES
-
The effect of the planar and central chirality of 1,2-(α-(N,N-dimethylamino)alkyl)formylcymantrene on the chromatographic properties of diastereomeric chelates of Cu2+ with Schiff bases from dipeptides and the aminoalkylformylcymantrenes, 1-(N,
- Tsiryapkin, V. A.,Loim, N. M.,Nedospasova, L. V.,Parnes, Z. N.,Belikov, V. M.,Kursanov, D. N.
-
-
