133373-24-7Relevant articles and documents
An efficient preparation of N-Methyl-α-amino acids from N-Nosyl-α-amino acid phenacyl esters
Leggio, Antonella,Belsito, Emilia Lucia,De Marco, Rosaria,Liguori, Angelo,Perri, Francesca,Viscomi, Maria Caterina
supporting information; experimental part, p. 1386 - 1392 (2010/06/11)
Chemical Equation Presented In this paper we describe a simple and efficient solution-phase synthesis of N-methyl-TV-nosyl-α-amino acids and N-Fmoc-N-methyl-α-amino acids. This represents a very important application in peptide synthesis to obtain N-methylated peptides in both solution and solid phase. The developed methodology involves the use of N-nosyl-α-amino acids with the carboxyl function protected as a phenacyl ester and the methylating reagent diazomethane. An important aspect of this synthetic strategy is the possibility to selectively deprotect the carboxyl function or alternatively both amino and carboxyl moieties by using the same reagent with a different molar excess and under mild conditions. Furthermore, the adopted procedure keeps unchanged the acid-sensitive side chain protecting groups used in Fmoc-based synthetic strategies.
Synthesis, conformational, properties, and antibody recognition of peptides containing β-turn mimetics based on α-alkylproline derivates
Hinds,Welsh,Brennand,Fisher,Glennie,Richards,Turner,Robinson
, p. 1777 - 1789 (2007/10/02)
Peptide recognition by monoclonal antibodies may provide a useful model for drug development, in particular to test the effects of conformational restriction on ligand binding. We have tested the influence of novel peptide mimetics upon conformation and binding affinity for the case of monoclonal antibodies raised to a peptide antigen which displays a preference for a β-turn conformation in aqueous solution. Two monoclonals were isolated that recognized the peptide Ac-Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala specifically at the β-turn formed by Tyr-Pro-Tyr-Asp. Peptide analogues were then synthesized containing mimetics designed to stabilize this conformation. One, analogue (3), contained a spirocyclic γ-lactam bridge between the α-position of proline-2 and the N atom of tyrosine-3, while another (2) contained (S)-α-methylproline at position 2. NMR spectroscopy and molecular modeling suggest that both analogues adopt reverse-turn conformations stablized relative to that in the native sequence. For the (S)-α-methylproline analogue binding to both monoclonal antibodies was substantially improved, compared with the native antigen, whereas the γ-lactam analogue (3) was not recognized by either antibody. Quantitative equilibrium ultrafiltration binding assays showed that the affinities of the (S)-α-methylproline analogue (2) for the two antibodies were improved over those measured with the native antigen by -2.3 and -0.65 kcal/mol. The origins of these free energy differences cannot be explained wholly on the basis of presumed extra hydrophobic contacts between the new methyl substituent and the antigen binding sites. We propose that the increased conformational stability of the analogue plays a decisive role, implying that the reverse turn detected in the native antigen, possibly a type-I turn, is important for recognition by the two antibodies.
