556-50-3Relevant articles and documents
THE PALLADIUM(II)-PROMOTED HYDROLYSIS OF METHYL AND ISOPROPYL GLYCYLGLYCINATE
Hay, Robert W.,Pujari, Mahesh P.
, p. 1083 - 1086 (1984)
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.
Mechanochemical Prebiotic Peptide Bond Formation**
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)
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.
En Route to a Heterogeneous Catalytic Direct Peptide Bond Formation by Zr-Based Metal-Organic Framework Catalysts
Conic, Dragan,De Azambuja, Francisco,Harvey, Jeremy N.,Loosen, Alexandra,Parac-Vogt, Tatjana N.,Van Den Besselaar, Maxime
, p. 7647 - 7658 (2021/06/30)
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.
Effect of high hydrostatic pressure on prebiotic peptide synthesis
Ying, Jianxi,Chen, Peng,Wu, Yile,Yang, Xu,Yan, Kaili,Xu, Pengxiang,Zhao, Yufen
supporting information, p. 367 - 370 (2018/06/18)
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.
Synthesis of Deuterated or Tritiated Glycine and Its Methyl Ester
Shevchenko,Andreeva,Nagaev, I. Yu.,Myasoedov
, p. 266 - 267 (2019/01/03)
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.
Superactivity of MOF-808 toward Peptide Bond Hydrolysis
Ly, Hong Giang T.,Fu, Guangxia,Kondinski, Aleksandar,Bueken, Bart,De Vos, Dirk,Parac-Vogt, Tatjana N.
, p. 6325 - 6335 (2018/05/14)
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.
Comparative study of the reactivity of zirconium(IV)-substituted polyoxometalates towards the hydrolysis of oligopeptides
Ly, Hong Giang T.,Absillis, Gregory,Parac-Vogt, Tatjana N.
, p. 2206 - 2215 (2015/05/13)
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.
Coupling-Reagent-Free Synthesis of Dipeptides and Tripeptides Using Amino Acid Ionic Liquids
Furukawa, Shinya,Fukuyama, Takahide,Matsui, Akihiro,Kuratsu, Mai,Nakaya, Ryotaro,Ineyama, Takashi,Ueda, Hiroshi,Ryu, Ilhyong
, p. 11980 - 11983 (2015/08/18)
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.
Kilogram-Scale Synthesis of Osteogenic Growth Peptide (10-14) Using a Fragment Coupling Approach
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)
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.
Identification and characterization of prokaryotic dipeptidyl-peptidase 5 from porphyromonas gingivalis
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)
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.
