- Large molecular assembly of amphotericin B formed in ergosterol-containing membrane evidenced by solid-state NMR of intramolecular bridged derivative
-
Amphotericin B (AmB 1) is known to assemble and form an ion channel across biomembranes. We have recently reported that conformation-restricted derivatives of AmB 2-4 show different ergosterol preferences in ion-channel assays, which suggested that the orientation of the mycosamine strongly affects the sterol selectivity of AmB. The data allowed us to assume that compound 3 showing the highest selectivity would reflect the active conformation of AmB in the channel assembly. In this study, to gain further insight into the active conformation of AmB, we prepared a new intramolecular-bridged derivative 5, where the linker encompassed a hydrophilic glycine moiety. The derivative has almost equivalent ion-channel activity to those of AmB and 3. The antifungal activity of 5 compared with 3 improves significantly, possibly because the increasing hydrophilicity in the linker enhances the penetrability through the fungal cell wall. Conformation of 5 was well converged and very similar to that of 3, thus further supporting the notion that the conformations of these derivatives reproduce the active structure of AmB in the channel complex. Then we used the derivative to probe the mobility of AmB in the membrane by solid-state NMR. To measure dipolar couplings and chemical shift anisotropies, we incorporated [1-13C,15N]glycine into the linker. The results indicate that 5 is mostly immobilized in ergosterol-containing DMPC bilayers, implying formation of large aggregates of 5. Meanwhile some fraction of 5 remains mobile in sterol-free DMPC bilayers, suggesting promotion of Amb aggregation by ergosterol.
- Matsumori, Nobuaki,Sawada, Yuri,Murata, Michio
-
-
Read Online
- Fmoc-Amox, A Suitable Reagent for the Introduction of Fmoc
-
Synthesis of most peptides is achieved using solid-phase peptide synthesis employing the Fmoc/tert-butyl strategy. However, the introduction of Fmoc in N-unprotected amino acids seems to be challenging due to the formation of dipeptides and sometimes tripeptides as impurities and β-alanyl impurities when Fmoc-OSu is used as well. Herein, we report an efficient and successful method using Fmoc-Amox, which is an oxime based derivative, toward the synthesis of Fmoc-glycine with no traces of side reactions. Fmoc-Amox is inexpensive, and Amox can be easily removed after the reaction, thus affording pure Fmoc-Gly-OH devoid of any detrimental impurities or contamination, mainly dipeptide or Amox itself, as shown by high-performance liquid chromatography and NMR, respectively.
- Kumar, Ashish,Sharma, Anamika,Haimov, Elvira,El-Faham, Ayman,De La Torre, Beatriz G.,Albericio, Fernando
-
-
Read Online
- Synthesis and characterization of a photocleavable collagen-like peptide
-
A 34-amino acid long collagen-like peptide rich in proline, hydroxyproline, and glycine, and with four photoreactive N-acyl-7-nitroindoline units incorporated into the peptide backbone was synthesized by on-resin fragment condensation. Its circular dichroism supports a stable triple helix structure. The built-in photochemical function enables the decomposition of the peptide into small peptide fragments by illumination with UV light of 350 nm in aqueous solution. Illumination of a thin film of the peptide, or a thin film of a photoreactive amino acid model compound containing a 5-bromo-7-nitroindoline moiety, with femtosecond laser light at 710 nm allows for the creation of well-resolved micropatterns. The cytocompatibility of the peptide was demonstrated using human mesenchymal stem cells and mouse embryonic fibroblasts. Our data show that the full-length peptide is cytocompatible as it can support cell growth and maintain cell viability. In contrast, the small peptide fragments created by photolysis are somewhat cytotoxic and therefore less cytocompatible. These data suggest that biomimetic collagen-like photoreactive peptides could potentially be used for growing cells in 2D micropatterns based on patterns generated by photolysis prior to cell growth.
- Li, Chunqiang,Ornelas, Alfredo,Williams, Kaitlyn N.,Hatch, Kevin A.,Paez, Aurelio,Aguilar, Angela C.,Ellis, Cameron C.,Tasnim, Nishat,Ray, Supriyo,Dirk, Carl W.,Boland, Thomas,Joddar, Binata,Michael, Katja
-
-
Read Online
- Oxime carbonates: Novel reagents for the introduction of fmoc and alloc protecting groups, free of side reactions
-
Fmoc and Alloc protecting groups represent a consistent alternative to classical Boc protection in peptide chemistry. The former was established in the last decades as the α-amino protecting group of choice, whereas the latter allows a fully orthogonal protection strategy with Fmoc and Boc. Usually, the introduction of the Fmoc and Alloc moieties takes place through their halogenoformates, azides, or activated carbonates. This rather simple reaction is accompanied by several side reactions, specially the formation of Fmoc/Alloc dipeptides and even tripeptides. The present work describes new promising Fmoc/Alloc-oxime reagents, which are easy to prepare, stable, and highly reactive crystalline materials that afford almost: contaminant-free Fmoc/Alloc-amino acids in high yields by following a conventional procedure. Amongst the Fmoc-oxime derivatives, the N-hydroxypicolimmidoyl cyanide derivative (N-([(9H-fluoren-9-yl)methoxy]carbonyloxy}picolinimidoyl cyanide) gave the best results for the preparation of Fmoc-Gly-OH, which is the most predisposed to give side reactions. The same Alloc-oxime analogue afforded the preparation of Alloc-Gly-OH in good yield, purity, and extremely low dipeptide formation, as analyzed by reverse-phase HPLC and NMR spectroscopy.
- Khattab, Sherine N.,Subiros-Funosas, Ramon,El-Faham, Ayman,Albericio, Fernando
-
-
Read Online
- Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
-
Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.
- Einsiedler, Manuel,Jamieson, Cooper S.,Maskeri, Mark A.,Houk, Kendall N.,Gulder, Tobias A. M.
-
supporting information
p. 8297 - 8302
(2021/03/01)
-
- A 4-OTBS benzyl-based protective group for carboxylic acids
-
Reported herein is a novel 4-OTBS benzyl-based protective group for carboxylic acids. This protective group can be removed in the presence of TBAF or TFA with high efficiency, which makes it compatible with base-sensitive or acid-sensitive substrates. With this protective group, a near-infrared fluorogenic probe for the detection of γ-glutamyltranspeptidase activities was readily prepared.
- Fang, Zhijun,Li, Yuyao,Xie, Hexin
-
supporting information
p. 1658 - 1662
(2019/05/29)
-
- Dihydroartemisinin and steroid conjugates, and preparation method and application thereof
-
The present invention discloses conjugates, having a general formula (I), obtained by condensation of dihydroartemisinin and steroids, or isomers or pharmaceutically acceptable salts or prodrug molecules thereof. The 10-position hydroxyl group of artemisinin and the 3-position hydroxyl group of the steroid compounds are condensed and linked by an ether bond. The invention discloses a preparation method of the compounds, and an application of the compounds in the treatment of autoimmune diseases. The dihydroartemisinin and steroid conjugates of the present invention are novel immunosuppressants, and can be used alone or in combination with other drugs to treat the human autoimmune diseases. The conjugates have the advantages of high curative effect, small toxicity and very broad applicationprospect.
- -
-
Paragraph 0098-0102
(2019/11/20)
-
- Unwanted hydrolysis or α/β-peptide bond formation: How long should the rate-limiting coupling step take?
-
Nowadays, in Solid Phase Peptide Synthesis (SPPS), being either manual, automated, continuous flow or microwave-assisted, the reaction with various coupling reagents takes place via in situ active ester formation. In this study, the formation and stability of these key active esters were investigated with time-resolved 1H NMR by using the common PyBOP/DIEA and HOBt/DIC coupling reagents for both α- and β-amino acids. Parallel to the amide bond formation, the hydrolysis of the α/β-active esters, a side reaction that is a considerable efficacy limiting factor, was studied. Based on the chemical nature/constitution of the active esters, three amino acid categories were determined: (i) the rapidly hydrolyzing ones (t 24 h) in solution. The current insight into the kinetics of this key hydrolysis side reaction serves as a guide to optimize the coupling conditions of α- and β-amino acids, thereby saving time and minimizing the amounts of reagents and amino acids to be used-all key factors of more environmentally friendly chemistry.
- Goldschmidt G?z, Viktória,Nagy, Adrienn,Farkas, Viktor,Keszei, Ern?,Perczel, András
-
p. 30720 - 30728
(2019/10/28)
-
- PHOTOREACTIVE COLLAGEN-LIKE PEPTIDES
-
A novel 34 amino acid long collagen-like peptide rich in proline, hydroxyproline, and glycine, and with several photoreactive N-acyl-7-nitroindoline units incorporated into the peptide backbone was synthesized by on-resin fragment condensation. The circular dichroism measurement of this peptide supports a stable triple helix structure. This peptide has potential as a new biomimetic material with built-in latent photochemical functions that enable the decomposition into small peptide fragments by illumination with UV light of 350 nm. Using a photoreactive glycine derivative as a model compound for the collagen-like peptide, we demonstrate that its photolysis can also be triggered by a two-photon absorption process using a femtosecond laser at 710 nm. When a thin film of this compound is irradiated with femtosecond laser light at 710 nm the photochemistry occurs only at locations of irradiation. In addition, the collagen-like peptide is able to support mesenchymal stem cell growth, indicating its non-toxicity to these cells and its potential in tissue engineering applications.
- -
-
Paragraph 0092
(2019/04/30)
-
- A colourful azulene-based protecting group for carboxylic acids
-
An intensely blue-coloured protecting group for carboxylic acids has been developed. The protecting group is introduced through a Steglich esterification that couples 6-(2-hydroxyethyl)azulene (AzulE) and the carboxylic acid substrate. Deprotection is effected under basic conditions by the addition of the amidine base DBU, whereupon cleavage occurs, accompanied by a colour change. A two-step deprotection methodology comprising activation with oxalyl chloride and deprotection with a very mild base was developed for use with base-sensitive substrates. The AzulE esters were found to be compatible with other commonly employed protecting groups – silyl ethers, MOM acetals – by studying their orthogonal and concomitant deprotections. The stability of the new protecting group towards various synthetic processes – oxidation, reduction, cross-coupling, olefination and treatment with base – provided the basis of a versatility profile. This indicated that AzulE esters are sensitive to strongly oxidising and basic agents while being compatible with reducing conditions and selected other reactions. The convenience of a highly coloured protecting group for tracking material (and avoiding loss of compound) through laboratory processes warrants further investigation of this and/or related species.
- Bevan, Thomas W.,Francis-Taylor, James,Wong, Helena,Northcote, Peter T.,Harvey, Joanne E.
-
supporting information
p. 2942 - 2955
(2018/05/16)
-
- Fmoc-OPhth, the reagent of Fmoc protection
-
Fmoc-OSu has been widely used for Fmoc protection of amino groups, especially amino acids, in solid phase peptide synthesis. However, it has been recognized that Fmoc-βAla-OH is formed as a by-product via the Lossen rearrangement during the reaction. Since we reconfirmed the formation of Fmoc-βAla-OH during the preparation of Fmoc-AA-OH by Fmoc-OSu, Fmoc-OPhth was designed and synthesized as a new Fmoc reagent to avoid the formation of Fmoc-βAla-OH. Furthermore, Fmoc protection by Fmoc-OPhth and Fmoc-SPPS were evaluated. The various Fmoc-amino acids prepared by Fmoc-OPhth were carried out in good yields and these are applicable in Fmoc-SPPS.
- Yoshino, Ryo,Tokairin, Yoshinori,Kikuchi, Mari,Konno, Hiroyuki
-
supporting information
p. 1600 - 1603
(2017/04/03)
-
- Synthesis and biological evaluation of novel FK228 analogues as potential isoform selective HDAC inhibitors
-
Novel C4- and C7-modified FK228 analogues were efficiently synthesized in a highly convergent and unified manner. This synthesis features the amide condensation of glycine-d-cysteine-containing segments with d-valine-containing segments for the direct assembly of the corresponding seco-acids, which are key precursors of macrolactones. The HDAC inhibition assay and cell-growth inhibition analysis of the synthesized analogues revealed novel aspects of their structure-activity relationship. This study demonstrated that simple modification at the C4 and C7 side chains in FK228 is effective for improving both HDAC inhibitory activity and isoform selectivity; moreover, potent and highly isoform-selective class I HDAC1 inhibitors were identified.
- Narita, Koichi,Matsuhara, Keisuke,Itoh, Jun,Akiyama, Yui,Dan, Singo,Yamori, Takao,Ito, Akihiro,Yoshida, Minoru,Katoh, Tadashi
-
p. 592 - 609
(2016/07/06)
-
- A kind of amino acid tanshinone phenolic derivative and its preparation method
-
The invention relates to amino acid tanshinone phenolic ester derivatives and a preparation method thereof. The derivatives are obtained by reducing tanshinone compounds and performing esterified modification on the reduced tanshinone compounds and an amino acid into prodrugs, wherein the tanshinone compounds are phenanthrenequinone compounds which exist in salvia miltiorrhiza and have an o-quinone structure; the esterified amino acid is alpha-amino acid. The amino acid tanshinone phenolic ester derivatives are compounds having a structure of a general formula (I) or medicinal salts thereof, wherein R1 and R2 represent H or acyl alpha-amino acid and a salt thereof, and R1 and R2 are not H at the same time. The amino acid tanshinone phenolic ester derivatives have the beneficial effects that firstly, the new tanshinone derivatives are provided and the new substances have potential treatment effect on some serious diseases such as tumors, and secondly, amino acid tanshinone phenolic ester derivatives have excellent water solubility and thus can be prepared into injections conveniently in addition to various oral preparations, and therefore, the amino acid tanshinone phenolic ester derivatives are capable of quickly taking effect in disease treatment. As important prodrugs, the amino acid tanshinone phenolic ester derivatives have important application value.
- -
-
Paragraph 0165
(2016/10/09)
-
- Glycine derivative corrosion inhibitor and preparation method thereof
-
The invention discloses a glycine derivative corrosion inhibitor. A preparation method of glycine derivative corrosion inhibitor comprises the following steps: (1) adding glycine and Fmoc-OSu into a DMF (Dimethyl Formamide) solvent for reaction, then adding an NaHCO3 remove solvent and residual amine compounds, and carrying out vacuum drying at 50 DEG C, thus obtaining Fmoc-glycine; (2) adding the Fmoc-glycine into CH2Cl2, adding SOCl2 under a protection condition of N2, and reacting for 4 hours at 50 DEG C, thus obtaining Fmoc-glycine chloride; (3) adding octadecylamne and a CH2Cl2 solution in the Fmoc-glycine chloride, then adding anhydrous sodium carbonate, and reacting for 4 hours at 50 DEG C, thus obtaining yellow solid. According to the glycine derivative corrosion inhibitor and the preparation method, disclosed by the invention, glycine molecules are connected to an Fmoc-protecting group and a hydrophobic long chain, so that the glycine molecules are adsorbed to metal through heteroatoms and double benzene rings containing pi electrons, water molecules are blocked by the hydrophobic long chain, a protection film is formed on the surface of steel, and an anti-corrosion purpose is achieved.
- -
-
Paragraph 0027; 0028
(2016/12/01)
-
- Site-selective chemical cleavage of peptide bonds
-
Site-selective cleavage of extremely unreactive peptide bonds is a very important chemical modification that provides invaluable information regarding protein sequence, and it acts as a modulator of protein structure and function for therapeutic applications. For controlled and selective cleavage, a daunting task, chemical reagents must selectively recognize or bind to one or more amino acid residues in the peptide chain and selectively cleave a peptide bond. Building on this principle, we have developed an approach that utilizes a chemical reagent to selectively modify the serine residue in a peptide chain and leads to the cleavage of a peptide backbone at the N-terminus of the serine residue. After cleavage, modified residues can be converted back to the original fragments. This method exhibits broad substrate scope and selectively cleaves various bioactive peptides with post-translational modifications (e.g. N-acetylation and -methylation) and mutations (d- and β-amino acids), which are a known cause of age related diseases.
- Elashal, Hader E.,Raj, Monika
-
supporting information
p. 6304 - 6307
(2016/05/24)
-
- USE OF COMPOSITIONS OBTAINED BY CALCINING PARTICULAR METAL-ACCUMULATING PLANTS FOR IMPLEMENTING CATALYTICAL REACTIONS
-
The use of metal-accumulating plants for implementing chemical reactions especially catalytical reactions.
- -
-
Paragraph 0626; 0627
(2016/01/25)
-
- A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids
-
The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of N-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that tert-butyloxycarbonyl (Boc), tert-butyl (tBu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding C-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective N-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected dipeptidyl diazoketones.
- Siciliano, Carlo,De Marco, Rosaria,Guidi, Ludovica Evelin,Spinella, Mariagiovanna,Liguori, Angelo
-
p. 10575 - 10582
(2013/02/22)
-
- New TFA-free cleavage and final deprotection in Fmoc solid-phase peptide synthesis: Dilute HCl in fluoro alcohol
-
A novel method for cleaving from resin and removing acid-labile protecting groups for the Fmoc solid-phase peptide synthesis is described. 0.1 N HCl in hexafluoroisopropanol or trifluoroethanol cleanly and rapidly removes the tert-butyl ester and ether, Boc, trityl, and Pbf groups and cleaves the common resin linkers: Wang, HMPA, Rink amide, and PAL. Addition of just 5-10% of a hydrogen-bonding solvent considerably retards or even fully inhibits the reaction. However, a non-hydrogen-bonding solvent is tolerated.
- Palladino, Pasquale,Stetsenko, Dmitry A.
-
supporting information
p. 6346 - 6349
(2013/02/25)
-
- Cyanoacetamide-based oxime carbonates: An efficient, simple alternative for the introduction of Fmoc with minimal dipeptide formation
-
Nowadays, most peptides are chemically achieved by using the Fmoc/tBu protection strategy, due to its fully orthogonal character, mild temporary group removal and resin cleavage steps. However, its introduction into N-unprotected amino acids is not exempt of synthetic inconveniences, such as dipeptide formation. Lately, novel oxime carbonates were introduced in the arsenal of reagents for the introduction of Fmoc, presenting almost negligible percentage of side-products. Herein, an enforced version of this family of Fmoc-carbonates is presented, containing stable and highly acidic cyanoacetamide-based oximes as leaving group. Such reactive species, affordable in only two steps from simple, readily available starting materials, show unusual ability to obtain the corresponding Fmoc-protected residues in high yield and minimal impact of detrimental side-products, mainly Fmoc-dipeptides.
- Khattab, Sherine N.,Subirós-Funosas, Ramon,El-Faham, Ayman,Albericio, Fernando
-
experimental part
p. 3056 - 3062
(2012/06/01)
-
- NOVEL PEPTIDES DERIVED FROM NCAM (FGLs)
-
The present invention relates to novel compounds comprising at most 13 contiguous amino acid residues derived from the fibronectin type 3,I1 module of neural cell adhesion molecule (NCAM), or a variant or fragment thereof, capable of interacting with an FGFR and thereby the compounds are capable of inducing differentiation, modulating proliferation, stimulate regeneration, neuronal plasticity and/or survival of cells. Further, the present invention relates to the use of said compounds for production of a medicament for treatment of conditions and diseases, wherein NCAM and/or FGFR play a prominent role.
- -
-
-
- An efficient and expeditious Fmoc protection of amines and amino acids in aqueous media
-
A new and environmentally friendly Fmoc protection of a variety of aliphatic and aromatic amines, amino acids, amino alcohols and amino phenols is reported in aqueous media under mild and catalyst-free conditions. The reaction proved to be chemoselective in presence of ambident nucleophiles.
- Gawande, Manoj B.,Branco, Paula S.
-
supporting information; experimental part
p. 3355 - 3359
(2012/01/06)
-
- Liquid-chromatography quantitative analysis of 20 amino acids after derivatization with FMOC-CI and its application to different origin Radix isatidis
-
We developed a simple, rapid and reliable method for determination of 20 common amino acids based on derivatization with 9-fluorenylmethyl chloroformate (FMOC-CI) and RP-LC/UV, this method was first introduced into quantitative analysis of amino acids. The amino groups of amino acids were trapped with FMOC-CI to form amino acid-FMOC-Cl adducts which can be suitable for LC-UV. Chromatographic separation was performed on a C18 column with a mobile phase gradient consisting of acetonitrile and sodium acetate solution. This method was shown to be sensitive for 20 common amino acids. In the intra-day precisions assay, the range of RSDs was 3.21-7.67% with accuracies of 92.34-102.51%; for the inter-day precisions assay, the range of RSDs was 5.82-9.19% with accuracies of 90.25-100.63%. The results also indicated that solutions of amino acids-FMOC-Cl can be kept at room temperature for at least 24 h without showing significant losses in the quantified values. The validated method was successfully applied to the determination of major four kinds of amino acids in R. isatidis samples (Arg, Pro, Met and Val). The total content of amino acids in different origin R. isatidis was 13.32-19.16 mg/g. The differences between R. isatidis samples were large using HCA.
- Zhou, Wei,Zhang, Xiao-Yan,Duan, Geng-Li
-
experimental part
p. 509 - 515
(2012/01/04)
-
- Benzotriazole reagents for the syntheses of Fmoc-, Boc-, and Alloc-protected amino acids
-
Stable Fmoc-, Boc-, and Alloc-benzotriazoles react with various amino acids including unprotected serine and glutamic acid, in the presence of triethylamine at 20° as reagents to introduce -amino protecting groups to afford Fmoc-, Boc-, and Alloc-protected amino acids (77-94%) free of dipeptide and tripeptide impurities. Fmoc-, and Alloc-Gly-Gly-OH dipeptides were prepared in 90% yields by N-acylation of glycylglycine with Fmoc- and Alloc-benzotriazoles in the presence of triethylamine. Synthesized N-protected amino acids were greater than 99% pure, analyzed by HPLC. Georg Thieme Verlag Stuttgart - New York.
- Ibrahim, Tarek S.,Tala, Srinivasa R.,El-Feky, Said A.,Abdel-Samii, Zakaria K.,Katritzky, Alan R.
-
p. 2013 - 2016
(2011/10/08)
-
- Basic techniques of working on a solid phase: From ABC of the peptide synthesis to libraries of non-natural amino acids
-
Libraries of hardly available amino acids bearing a heteroaromatic ring (2-pyrimidyl, substituted 2-pyridyl or 2-thiazolyl) at the amino group were prepared using solid-phase synthesis on various resins. The synthesized compounds are structurally similar to some known antidiabetic drugs. The paper combines features of a review (elementary introduction to the solid-phase synthesis methodology and technique for beginners and selected methods from peptide chemistry) and step-by-step experimental protocols (tested by the authors) useful as a methodic tool. The presented protocols (immobilization and modification of amino acids, placing and removal of common protective groups) require no sophisticated equipment and may be useful as pictorial introductory tasks for students education. Pleiades Publishing, Ltd., 2010.
- Babaev,Ermolat'ev
-
experimental part
p. 2572 - 2589
(2011/04/15)
-
- Reversible hydrogen transfer between cysteine thiyl radical and glycine and alanine in model peptides: Covalent H/D exchange, radical-radical reactions, and l - To D -Ala conversion
-
The reversible intramolecular hydrogen transfer reaction of peptide Cys thiyl radicals with Gly and Ala residues was studied in model peptides, where thiyl radicals were either generated through photochemical cleavage of disulfide bonds or through the rea
- Mozziconacci, Olivier,Kerwin, Bruce A.,Sch?neich, Christian
-
experimental part
p. 6751 - 6762
(2011/01/03)
-
- Efficient procedure for the preparation of oligomer-free N-fmoc amino acids
-
A two-step method is presented for the peptide-free, high-purity, and high-yield synthesis of N-Fmoc amino acids. The first step involves the preparation of stable dicyclohexylammonium-amino acid ionic adduct in acetone. Subsequently, the ionic adducts, on reaction with Fmoc-Nosu under mild alkaline conditions, give dipeptide-free N-Fmoc amino acids. The positive charge of the dicyclohexylammonium counterion in the ionic salt has a longer radius, moderating the nucleophilicity of the carboxylate ion of the amino acid and preventing by-products by arresting the formation of mixed anhydrides, the precursors of oligopeptide impurities.
- Nowshuddin, Shaik,Rao,Reddy, A. Ram
-
experimental part
p. 2022 - 2031
(2009/11/30)
-
- Novel fused pyrazolyl compounds having an aminoalkylcarbonyl group
-
A fused pyrazolyl compound having an anti-tumor potency of the following formula is synthesized: wherein A is in which n is 0, 1, 2, or 3; Ar1 is benzene, thiophene or furan; Ar2 is furyl; and Ar3 is phenyl; R1 and R2 independently are hydrogen, halogen or —(CH2)mORe; R3 is hydrogen or alkyl; R4 is —(CH2)r-A1, wherein r is an integer of 1-5, and A1 has a formula of —O—C(O)—(CRcH)q—NRc′Rd′; R5 and R6 independently are hydrogen, halogen, or alkyl, or R5 and R6 together are —O(CH2)mO—; Rc is H, halogen, nitro, cyano, alkyl, or aryl; Re is H, alkyl, or aryl; Rc′ and Rd′ independently are H, alkyl, or aryl; m is 0, 1, 2, 3, 4, 5, or 6; and q is 1, 2, 3, 4, 5, or 6; or a salt thereof.
- -
-
Page/Page column 2
(2009/05/28)
-
- Useful reagents for introduction of Boc and Fmoc protective groups to amines: Boc-DMT and Fmoc-DMT
-
New amino-protecting reagents, Boc-DMT and Fmoc-DMT, were prepared, and found to be useful for the introduction of Boc and Fmoc groups into amines. Both the reagents can protect various amines including amino acids in good yield in aqueous media. Since the reagents are neither unstable nor irritating, they are practically useful. Georg Thieme Verlag Stuttgart.
- Hioki, Kazuhito,Kinugasa, Mizuho,Kishimoto, Michiko,Fujiwara, Miho,Tani, Shohei,Kunishima, Munetaka
-
p. 1931 - 1933
(2007/10/03)
-
- Fluorogenic ester substrates to assess proteolytic activity
-
The synthesis of a new type of fluorogenic ester substrates is described. Prepared from fluorescein in three steps with common commercially available precursors, they all generate bright green fluorescence upon proteolysis. Their particular structure allows the same substrate be used to report enzymatic activity of various proteases from serine and cysteine superfamilies. The substrate cleavage is sensitive to specific protease inhibitors providing a tool for inhibitor screening.
- Mugherli, Laurent,Burchak, Olga N.,Chatelain, Francois,Balakirev, Maxim Y.
-
p. 4488 - 4491
(2007/10/03)
-
- Synthesis of Fmoc-protected β-amino alcohols and peptidyl alcohols from Fmoc-amino acid/peptide acid azides
-
An efficient synthesis of Nα-9H-fluoren-9- ylmethoxycarbony(Fmoc)-β-amino alcohols by the reduction of Fmoc-α-amino acyl azides employing aqueous NaBH4 as a reducing agent has been described. The reduction is found to be simple and almost complete. All the Fmoc-β-amino alcohols prepared are fully characterized by 1H and 13C NMR and mass spectrometry. Further, the method is extended for the reduction of seven Fmoc-dipeptidyl acids to the corresponding alcohols. Their reduction is also found to be smooth and complete.
- Babu, Vommina V. Suresh,Kantharaju,Sudarshan, Naremaddepalli S.
-
p. 1880 - 1886
(2007/10/03)
-
- Enzyme-cleavable linkers for peptide and glycopeptide synthesis
-
Hydroxymethylphenoxy linkers that are commonly used in solid phase peptide synthesis are surprisingly susceptible to efficient cleavage by the protease chymotrypsin with a broad range of amino acid residues being tolerated at the scissile bond; this enzyme-cleavable linker system has been applied to peptide and glycopeptide synthesis. The Royal Society of Chemistry 2005.
- Maltman, Beatrice A.,Bejugam, Mallesham,Flitsch, Sabine L.
-
p. 2505 - 2507
(2007/10/03)
-
- GLP-2 compounds, formulations, and uses thereof
-
The present invention relates to novel human glucagon-like peptide-2 (GLP-2) peptides and human glucagon-like peptide-2 derivatives which have a protracted profile of action as well as polynucleotide constructs encoding such peptides, vectors and host cells comprising and expressing the polynucleotide, pharmaceutical compositions, uses and methods of treatment.
- -
-
-
- One-pot preparation of N-carbamate protected amino acids via the azide
-
A convenient and efficient method for the preparation of fluorenylmethyloxycarbonyl (Fmoc) and allyloxycarbonyl (Alloc) amino acids is proposed. This method is particularly attractive due to the fact that the reaction sequence Fmoc/Alloc-chloride to Fmoc/Alloc-azide to Fmoc/Alloc-amino acid can readily be carried out in one pot. A further advantage is the minimization of byproducts, which are easily removed during the workup. Most important, this strategy minimizes the formation of dipeptides that are difficult to remove by crystallization. Thus, Fmoc and Alloc amino acids are obtained in high yield (60-90%) and purity as evidenced by thin-layer chromatography, reversed-phase high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance.
- Cruz, Luis J.,Beteta, Natalia G.,Ewenson, Ariel,Albericio, Fernando
-
p. 920 - 924
(2013/09/03)
-
- Method for preparing a ligand presenting assembly (LPA), an LPA and uses thereof
-
The present invention relates to a method for preparing a ligand presenting assembly (LPA), an LPA, an immunological composition and a vaccine. The invention further relates to a method for generating antibodies, a kit for use in diagnosis and use of an LPA for preparing a pharmaceutical composition.
- -
-
-
- 1-[2-(2-Hydroxyalkyl)phenyl]ethanone: A New Photoremovable Protecting Group for Carboxylic Acids
-
(Equation presented) A new photoremovable protecting group for carboxylic acids is introduced. The protecting group 1-[2-(2-hydroxyalkyl)phenyl]ethanone, HAPE, is used to protect various carboxylic acids. When photolyzed, the protected compound releases the acid in 70-85% isolated yields. The synthesis and the results of photorelease of the protected acids are presented here.
- Atemnkeng, Walters N.,Louisiana II, Larry D.,Yong, Promise K.,Vottero, Breanne,Banerjee, Anamitro
-
p. 4469 - 4471
(2007/10/03)
-
- LIGAND PRESENTING ASSEMBLY (LPA), METHOD OF PREPARATION AND USES THEREOF
-
The present invention relates to a method for preparing a ligand presenting assembly (LPA), an LPA, an immunological composition and a vaccine. The invention further relates to a method for generating antibodies, a kit for use in diagnosis and use of an LPA for preparing a pharmaceutical composition.
- -
-
-
- Nucleophile-stable thioester generating compounds, methods of production and use
-
The invention is directed to nucleophile-stable thioester generating compounds comprising an orthothioloester or a carboxyester thiol, methods of production and use. The compounds and methods have wide applicability in organic synthesis, including the generation of peptide-, polypeptide- and other polymer-thioesters. The invention is particularly useful for generating activated-thioesters from precursors that are made under conditions in which strong nucleophiles are employed, such as peptides or polypeptides made using Fmoc SPPS, as well as multi-step ligation or conjugation schemes that require (or benefit from the use of) compatible selective approaches for directing a specific ligation or conjugation reaction of interest.
- -
-
-
- Isoquinoline derivatives and isoquinoline combinatorial libraries
-
The present invention provides the synthesis of heterocyclic compounds based on the isoquinoline ring. More specifically, the invention provides novel isoquinoline derivatives as well as novel libraries comprised of such compounds.
- -
-
-
- A new polymer-supported reagent for the Fmoc-protection of amino acids
-
A new polymer-supported Fmoc-OSu (Fmoc-P-OSu) has been prepared from polymer-bound N-hydroxysuccinimide (P-HOSu), and used as a solid-supported reagent for the Fmoc-protection of amino groups. The residual P-HOSu generated after the protection reaction can be separated by simple filtration and reused.
- Chinchilla, Rafael,Dodsworth, David,Nájera, Carmen,Soriano, José
-
p. 7579 - 7581
(2007/10/03)
-
- Isoquinoline derivatives and isoquinoline combinatorial libraries
-
The present invention provides the synthesis of heterocyclic compounds based on the isoquinoline ring. More specifically, the invention provides novel isoquinolines as well as novel libraries comprised of many such compounds, and methods of synthesizing the libraries.
- -
-
-
- ISOQUINOLINE DERIVATIVES AND ISOQUINOLINE COMBINATORIAL LIBRARIES
-
The present invention provides the synthesis of heterocyclic compounds based on the isoquinoline ring. More specifically, the invention provides novel isoquinolines as well as novel libraries comprised of many such compounds, and methods of synthesizing the libraries.
- -
-
-
- Apparatus and methods for detecting antibodies
-
A single, unitary, solid phase support apparatus having a planar surface divided into a plurality of separate zone functions to detect antibodies. Each zone has bonded to it, a different peptide through its C-terminal end. The zones are incubated with the analyte sample and observed for reaction, indicating the virus-specific or bacteria specific presence or absence.
- -
-
-
- Syntheses and transglutaminase-catalyzed incorporation of novel spin-labeled primary amines into proteins
-
A series of spin-labeled primary amine derivatives, namely, 2,2,6,6-tetramethyl-piperidinyl-oxyl-4-amidoalkylamines with varying alkyl chain lengths, have been synthesized. The spin-labeled primary amine-with a tetramethylene or a pentamethylene chain covalently modifies human plasma fibronectin with a stoichiometry of 0.97-to-1.0 (probe-to-subunit) in the presence of coagulation factor XIIIa. The labels with two or one methylene chain also similarly modify fibronectin, but with a stoichiometry of only about 0.3-0.4 per subunit. The spin-labeled primary amine with a trimethylene chain does not label fibronectin. The labeling site appears to be the glutamine-3 residue at the amino-terminal region of fibronectin. Electron spin resonance studies show that the bound labels are partially immobilized with an effective rotational correlation time of 0.4-0.6 ns. The spin-labeled primary amine with tetramethylene chain also is shown to covalently incorporate into bee venom melittin in the presence of guinea-pig liver transglutaminase. The syntheses of the various spin-labeled primary amines and their applications in the study of structure and dynamics of different proteins and peptides are discussed. The observations from this study suggest that these spin-labeled primary amines have potentially wide application as structural probes.
- Narasimhan, Chakravarthy,Lai, Ching-San,Joseph, Joy
-
-
- Potential formation of intramolecular inclusion complexes in peptidocyclodextrins as evidenced by NMR spectroscopy
-
Investigations of the structure of β- and γ-cyclodextrin derivatives in solution obtained by grafting amino acids or peptides are presented.These compounds are models for vectorization-dedicated molecular carriers.It is shown that for some amino acids, strong intramolecular self-inclusion complexes are formed in aqueous solution.This process strongly depends upon the nature and position of the pertinent amino acid in the peptide sequence.Two dimensional NMR experiments are used in conjunction with competition with external guests to evidence and estimate the strength of these auto-inclusion complexes.
- Djedaini-Pilard, Florence,Azaroual-Bellanger, Nathalie,Gosnat, Muriel,Vernet, Delphine,Perly, Bruno
-
p. 723 - 730
(2007/10/02)
-
- Process for production of sulfonium compounds
-
Process for production of sulfonium compounds represented by the general formula (III), comprising reacting p-dialkylsulfoniophenols represented by the general formula (I) and carbonyl halogenide compounds represented by the general formula (II) in the presence of secondary amine having the structure in which two secondary alkyl groups are linked to the nitrogen atom., General Formula (I): General Formula (II): General Formula (III): (all the symbols are as described in the appended claims).
- -
-
-
- 5-Norbornene-2,3-dicarboximido Carbonochloridate. A New Stable Reagent for the Introduction of Amino-Protecting Groups
-
The synthesis of activated carbonates, based on a new carbonochloridate derived from N-hydroxy-5-norbornene-2,3-dicarboximide, is reported.These activated carbonic esters are excellent reagents for the introduction of all currently used urethane protecting groups.
- Henklein, Peter,Heyne, Hans-Ulrich,Halatsch, Wolf-Rainer,Niedrich, Hartmut
-
p. 166 - 167
(2007/10/02)
-
- DIISOPROPYLETHYLAMINE ELIMINATES DIPEPTIDE FORMATION DURING THE ACYLATION OF AMINO ACIDS USING BENZOYL CHLORIDE AND SOME ALKYL CHLOROFORMATES
-
Acylation of amino acids using benzoyl chloride in aqueous alkali leads to benzoylamino acids containing one percent of benzoyldipeptide.Use of diisopropylethylamine instead of sodium hydroxide as base eliminates the side reaction responsible for the contaminant.Ethoxycarbonylamino acids are advantageously prepared in the same manner using ethyl chloroformate or diethyl dicarbonate.The latter gives rise to some N-substituted dipeptide when used in aqueous alkali.The method is unsatisfactory for the benzyloxycarbonylation of amino acids.Use of 9-fluorenylmethyl chloroformate and diisopropylethylamine gives the pure derivative of leucine in moderate yield.
- Chen, Francis M. F.,Benoiton, N. Leo
-
p. 1224 - 1227
(2007/10/02)
-
- 9-Fluorenylmethyl Pentafluorophenyl Carbonate as a Useful Reagent for the Preparation of N-9-Fluorenylmethyloxycarbonylamino Acids and their Pentafluorophenyl Esters
-
9-Fluorenylmethyl pentafluorophenyl carbonate is a useful reagent for the efficient, side reaction-free introduction of N-9-fluorenylmethyloxycarbonyl protecting group into amino acids and for the subsequent preparation of their pentafluorophenyl esters.Some new compounds of both types are described.
- Schoen, Istvan,Kisfaludy, Lajos
-
p. 303 - 305
(2007/10/02)
-
