1421-69-8Relevant academic research and scientific papers
One-step C-terminal deprotection and activation of peptides with peptide amidase from stenotrophomonas maltophilia in neat organic solvent
Arif, Muhammad I.,Toplak, Ana,Szymanski, Wiktor,Feringa, Ben L.,Nuijens, Timo,Quaedflieg, Peter J. L. M.,Wu, Bian,Janssen, Dick B.
, p. 2197 - 2202 (2014/07/21)
Chemoenzymatic peptide synthesis is a rapidly developing technology for cost effective peptide production on a large scale. As an alternative to the traditional C→N strategy, which employs expensive N-protected building blocks in each step, we have investigated an N→C extension route that is based on activation of a peptide C-terminal amide protecting group to the corresponding methyl ester. We found that this conversion is efficiently catalysed by Stenotrophomonas maltophilia peptide amidase in neat organic media. The system excludes the possibility of internal peptide cleavage as the enzyme lacks intrinsic protease activity. The produced peptide methyl ester was used for peptide chain extension in a kinetically controlled reaction by a thermostable protease.
A new benzotriazole-mediated stereoflexible gateway to hetero-2,5- diketopiperazines
Monbaliu, Jean-Christophe M.,Hansen, Finn K.,Beagle, Lucas K.,Panzner, Matthew J.,Steel, Peter J.,Todadze, Ekaterina,Stevens, Christian V.,Katritzky, Alan R.
supporting information; experimental part, p. 2632 - 2638 (2012/04/17)
Open chain Cbz-L-aa1-L-Pro-Bt (Bt=benzotriazole) sequences were converted into either the corresponding trans- or cis-fused 2,5- diketopiperazines (DKPs) depending on the reaction conditions. Thermodynamic tandem cyclization/epimerization afforded selectively the corresponding trans-DKPs (69-75%). Complementarily, tandem deprotection/cyclization led to the cis-DKPs (65-72%). A representative set of proline-containing cis- and trans-DKPs has been prepared. A mechanistic investigation, based on chiral HPLC, kinetics, and computational studies enabled a rationalization of the results. Stereoflexible route to DKPs: A convenient, versatile, and flexible benzotriazole-mediated methodology for the synthesis of proline-containing hetero-2,5-diketopiperazines (DKPs) is reported. Depending on the reaction conditions, either cis- or trans-configured DKPs were obtained starting from the same inexpensive l,l-dipeptidoyl benzotriazole key intermediate (see scheme). Kinetics, chiral HPLC, and computational studies forged a background for mechanistic rationalization. Copyright
Synthesis of dipeptides from N-hydroxy-3-azaspiro[5,5]undecane-2,4-dione activated α-amino acids
Nowshuddin, Shaik,Ram Reddy
experimental part, p. 22 - 25 (2011/04/18)
A simple two step procedure for the synthesis of a dipeptide from N-hydroxy-3-azaspiro[5,5]undecane-2,4-dione (HO-ASUD) activated α-amino acids is described. In presence of DCC, N-hydroxy-3-azaspiro[5,5]undecane-2,4- dione readily esterifies the carboxylic acid group of all the N-protected amino acids to yield crystalline N-hydroxy-3-aza spiro[5,5]undecane-2,4-dione activated carboxy ester. The N-hydroxy-3-aza spiro[5,5]undecane-2,4-dione activated carboxy esters of N-protected amino acids readily condensed with other amino acids and gave a dipeptide. This new method is effective for the DCC coupling of a variety of chiral amino acids without loss of enantiomeric purity. Synthesis of fifteen dipeptides including the hitherto unreported Fmoc-l-Orn(Boc)-Val-OMe, Fmoc-l-Cys(trt)-Gly-OEt and Boc-l-Tyr-Gly-OEt is presented.
Peptide coupling of unprotected amino acids through in situ p-nitrophenyl ester formation
Gagnon, Paul,Huang, Xicai,Therrien, Eric,Keillor, Jeffrey W.
, p. 7717 - 7719 (2007/10/03)
Several series of dipeptides and tripeptides were prepared via an activation-coupling method involving the in situ formation of a p-nitrophenyl ester of an (N-protected) amino acid, followed by coupling with an unprotected amino acid in partially aqueous solutions. The resulting peptide is easily isolated by precipitation. In general, the yields obtained are good to excellent and racemization is minimal. This method is particularly advantageous with respect to its simplicity and lack of obligatory side chain protection/deprotection steps.
Single-step enzymatic conversion of peptide amides to esters
Meos, Helle,Haga, Mati,Tougu, Vello
, p. 2343 - 2346 (2007/10/02)
It is shown that the C-terminal amide groups in N-protected peptides could be efficiently replaced by ester groups via kinetically-controlled papain-catalyzed acyl transfer reactions in aqueous methanol. The specificity of papain was substantially shifted towards the cleavage of C-terminal amide bond in dipeptide substrates by methanol, thus suppressing undesired peptide bond cleavage during esterification.
PEPTIDE SYNTHESIS CATALYZED BY NATIVE PROTEINASE K IN WATER-MISCIBLE ORGANIC SOLVENTS WITH LOW WATER CONTENT
Cerovsky, Vaclav,Martinek, Karel
, p. 2027 - 2041 (2007/10/02)
Rection of Ac-Tyr-OEt with HBr.Gly-NH2, catalysed by free proteinase K in various water-miscible organic solvents in the presence of triethylamine and 5 mol percent of water, was studied.Some aliphatic alcohols and acetonitrile proved to be suitable solvents.The effect of water content (2 percent - 20 percent) on the synthesis of Ac-Tyr-Gly-NH2 was studied using acetonitrile as solvent.Lowering of the water content to 5 percent or 2 percent led to almost 100 percent yield of the desired dipeptide; higher water content accelerated the reaction reducing at the same time the yield of Ac-Tyr-Gly-NH2 due to the concurrent hydrolysis of the ester Ac-Tyr-OEt.No reaction was observed in the absence of base (triethylamine), wereas an excess of base only retarded the reaction.The enzyme is capable of catalyzing the peptide bond synthesis with N-acylamino acids or N-acyl peptides as acylating components, which may contain all types of L-amino acid residues (except Pro) in the P1 position.However, the peptide bond synthesis depends strongly on the amino component composition, particularly on the amino acid residue in the P'1 position.Only amides of glycine and of hydrophillic amino acids were acylated with Ac-Tyr-OEt; amides of hydrophobic amino acids enter the reaction only reluctantly or not at al.The presence of Leu or Phe in position P'2 and Leu in position P'3 has not so negative effect on acylation of the amino component as has in presence in the P'1 position.The choice of protecting groups for the α-carboxyl of the amino component is restricted only to amide and in some cases its undesired enzymatic removal was observed.Unprotected peptides seem to be suitable amino components.
INVESTIGATION ON COUPLING PEPTIDES TO AMINOMETHYL POLYMERS
Orlowska, Alicja,Drabarek, Stefania
, p. 2329 - 2336 (2007/10/02)
Different peptide bond forming methods for attachment of model peptides to aminomethyl polymers have been compared.It has been observed that the yield of reaction depends on such features of polymer as quantity of functional groups and degree of its cross-linking.The sequential Edman degradation of a model peptide corresponding to 5 to 9 fragment of substance P was performed by the solid-phase technique.
