- A PROCESS FOR PREPARATION OF A PEPTIDE
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The present invention relates to a novel process for preparation of peptides having amino acid chain length in the range of 2-40 comprises the steps: i) attaching an end-blocked amino acid with an ionic liquid based solid support in presence of an ionic solvent to obtain an end-terminal blocked amino acid attached ionic liquid; ii) removing end-terminal blocking agent from the end-terminal blocked amino acid attached ionic liquid of step i) followed by work up to obtain an amino acid attached ionic liquid; iii) repeating steps i) through ii) one or more times to obtain a polypeptide attached ionic liquid; and iv) detaching the polypeptide from the polypeptide attached ionic liquid of step iii) to obtain the polypeptide. Said process does not use any auxiliary reagents like dehydrating agent or activating agent. The use of ionic liquids as supports as well as solvents result in the faster kinetics of the process, the separation issues are reduced, and the process has no racemization issues.
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Page/Page column 13-14; 15-16
(2018/07/29)
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- Asymmetric Michael addition organocatalyzed by α,β-dipeptides under solvent-free reaction conditions
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The application of six novel α,β-dipeptides as chiral organocatalysts in the asymmetric Michael addition reaction between enolizable aldehydes and N-arylmaleimides or nitroolefins is described. With N-arylmaleimides as substrates, the best results were achieved with dipeptide 2 as a catalyst in the presence of aq. NaOH. Whereas dipeptides 4 and 6 in conjunction with 4-dimethylaminopyridine (DMAP) and thiourea as a hydrogen bond donor proved to be highly efficient organocatalytic systems in the enantioselective reaction between isobutyraldehyde and various nitroolefins.
- Avila-Ortiz, C. Gabriela,Lenin, Diaz-Corona,Erika, Jiménez-González,Juaristi, Eusebio
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- Aggregation propensity of amyloidogenic and elastomeric dipeptides constituents
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This study demonstrates the self-assembly of N- and C-terminal protected dipeptides Phe–Gly and Pro–Gly which were derived from amyloidogenic and elastomeric peptide sequences. These constituents afforded nanostructured supramolecular ensembles through va
- Kumar, Vikas,Krishna, K. Vijaya,Khanna, Shruti,Joshi, Khashti Ballabh
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p. 5369 - 5376
(2016/08/05)
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- MgI2-Mediated Chemoselective Cleavage of Protecting Groups: An Alternative to Conventional Deprotection Methodologies
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The scope of MgI2 as a valuable tool for quantitative and mild chemoselective cleavage of protecting groups is described here. This novel synthetic approach expands the use of protecting groups, widens the concept of orthogonality in synthetic processes, and offers a facile opportunity to release compounds from solid supports. Amazing MgI2: Protecting groups have had a tremendous positive impact on the art of biomolecule synthesis. In a context in which the use of attractive protecting groups is often limited by harsh deprotection conditions and low chemoselective flexibility, MgI2 offers, by the execution of a very simple protocol, a fresh vision with extensive perspectives.
- Berthet, Mathéo,Davanier, Florian,Dujardin, Gilles,Martinez, Jean,Parrot, Isabelle
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supporting information
p. 11014 - 11016
(2015/11/10)
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- N -boc deprotection and isolation method for water-soluble zwitterionic compounds
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A highly efficient TMSI-mediated deprotection and direct isolation method to obtain zwitterionic compounds from the corresponding N-Boc derivatives has been developed. This method has been demonstrated in the final deprotection/isolation of the β-lactamase inhibitor MK-7655 as a part of its manufacturing process. Further application of this process toward other zwitterionic compounds, such as dipeptides and tripeptides, has been successfully developed. Furthermore, a catalytic version of this transformation has been demonstrated in the presence of BSA or BSTFA.
- Liu, Zhijian,Yasuda, Nobuyoshi,Simeone, Michael,Reamer, Robert A.
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p. 11792 - 11796
(2015/02/19)
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- Microbial enantioselective removal of the N-benzyloxycarbonyl amino protecting group
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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
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- Stereoselective ring contraction of 2,5-diketopiperazines: An innovative approach to the synthesis of promising bioactive 5-membered scaffolds
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Ring contraction of 2,5-diketopiperazines by TRAL-alkylation led us to the stereoselective synthesis of original pyrrolidine-2,4-diones, a novel series of promising molecules with moderate anti-proliferative activity on breast cancer cells.
- Coursindel, Thibault,Restouin, Audrey,Dewynter, Georges,Martinez, Jean,Collette, Yves,Parrot, Isabelle
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experimental part
p. 210 - 217
(2010/10/01)
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- Structure-activity relationships for dipeptide prodrugs of acyclovir: Implications for prodrug design
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A series of water-soluble dipeptide ester prodrugs of the antiviral acyclovir (ACV) were evaluated for their chemical stability, cytotoxicity, and antiviral activity against several strains of Herpes Simplex-1 and -2, vaccinia, vesicular stomatitis, cytom
- Santos, Cledir R.,Capela, Rita,Pereira, Claudia S.G.P.,Valente, Emilia,Gouveia, Luis,Pannecouque, Christophe,De Clercq, Erik,Moreira, Rui,Gomes, Paula
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body text
p. 2339 - 2346
(2009/12/07)
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- Rates of reduction of N-chlorinated peptides by sulfite: Relevance to incomplete dechlorination of wastewaters
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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.
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p. 516 - 522
(2007/10/03)
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- Optimisation of the retroracemisation procedure for α-amino acids using (S)-2-[(N-alkylprolyl)amino]benzophenones, recyclable chiral axiliaries
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The retroracemisation procedure developed by Belokon and coworkers has been re-examined using a variety of new (S)-2-[N-alkylprolyl)amino]benzophenone chiral auxiliaries. It has been found that (S)-2-[(N-benzylprolyl)amino] and (S)-2-[(N-1-(naphthalenyl-1-methyl)prolyl)amino] benzophenones ((S)-BPB and (S)-NPB) when used in conjunction with Ni(NO3)2·6H2O and a racemic α-amino acid preferentially form a single diastereoisomer in the presence of a mild base such as sodium methoxide. Decomposition of this complex under acidic conditions leads to the isolation of the (S)-amino acid in good yield, and in 55 to 99% e.e. The retroracemisation abilities of a polymer supported form of the (S)-BPB ligand have also been investigated and preliminary results for this are presented here.
- De, Binod B.,Thomas, Neil R.
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p. 2687 - 2691
(2007/10/03)
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- 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
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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
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p. 6813 - 6821
(2007/10/02)
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- SYNTHESIS AND CONFORMATION OF N-TRITYL DIPEPTIDE DERIVATIVES
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N-Tritylamino acids activated with DCC/HOBt, were coupled with various amino acid derivatives without racemization.The trityl group was split off quantitatively in 10percent CCl3COOH monohydrate or CH2ClCOOH in CH2Cl2
- Matsoukas, J.,Tsegenidis, Th.,Cordopatis, P.,Theodoropoulos, D.
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p. 1869 - 1872
(2007/10/02)
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- The Steric Hindrance of the Stepwise Reaction of N-Carboxy α-Amino Acid Anhydride with the α-Amino Acid Ester
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The mechanisms of the reactions of 4-alkyloxazolidinediones (1) (N-carboxy α-amino acid anhydrides(NCAs)) with α-amino acid benzyl ester p-toluenesulfonates (2) were investigated in acetonitrile containing triethylamine at low and room temperatures.Two types of reactions were observed: (1) the polymerization of NCAs was initiated with a small amount of 2 to produce polypeptides (6), and (2) the dipeptide benzyl esters (4) were produced by the stepwise reaction of NCAs with the esters.Both the polymerization and the dipeptide formation (1+2) seemed to be initiated by the nucleophilic attack of the amino group of the ester on the C-5 carbon of NCAs.The polymerization proceeded when the side chains of the amino acid esters (R2) were more bulky than those of the NCAs (R1).On the contrary, dipeptide esters were produced when the side chains of the NCAs (R1) were more bulky than those of the esters (R2).
- Oya, Masanao,Takahashi, Tomoko
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p. 2705 - 2707
(2007/10/02)
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- Peptides 119. - Peptide Synthesis with N-Carboxy-α-amino Acid Anhydrides
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On reaction of N-carboxy-α-amino acid anhydrides (NCA) with equimolar amounts of aminoacids or excess NCA in potassium borate buffer of pH 10.2 (0 deg C) considerable amounts of homooligomers and homopolymers are formed.If an excess of amino acid is used formation of the above mentioned by-products can be suppressed.The extent of homooligomerization and homopolymerization and hydrolysis occurring during the reaction of NCA under the conditions of peptide synthesis is described.
- Kircher, K.,Berndt, H.,Zahn, H.
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p. 275 - 284
(2007/10/02)
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