Conformational energy analysis of retro‐all‐Dmethionine enkephalin

Abstract

SynopsisEmpirical conformational energy calculations have been carried out on the molecule retro-all-D-methionine enkephalin. Low-energy conformers were found by energy minimization and conformational search procedures. The lowest energy conformers were found to have some stereochemical relationship to the calculated normal met-enkephalin conformers, but they were not retro-all-D-equivalent to the Met-enkephalin structures. The retro-all-D-equivalent conformations were -10 kcdmol higher energy than the low-energy conformers found here. A structural comparison between the retro-all-D-conformers and the met-enkephalin conformers shows that one cannot rely solely on topochemical analysis to predict biological activity for linear retro-all-D-peptides.

Solution Structures of FcεRI α-Chain Mimics: A β-Hairpin Peptide and Its Retroenantiomer

“…The d -peptide was designed to be a retroenantiomer of the l -amino acid peptide, presenting a similar topological surface as the l -peptide, while making use of the preferred pharmacological properties of d -amino acids. The underlying principles of the retro-inverso approach have been evident for many years. − In support of this theory, l - and retro- d -peptides have been shown to possess similar biological activities in a number of cases. , However this has not proven to be universally true. , The l - and retro- d -amino acid FcεRI peptide mimics were cyclized by an intramolecular disulfide bond formed between amino and carboxyl terminal cysteine residues. The remaining peptide sequence found in the mimics is native to the C−C‘ region of FcεRI α2.…”

“…5,16 However this has not proven to be universally true. 8,17 The L-and retro-D-amino acid Fc RI peptide mimics were cyclized by an intramolecular disulfide bond formed between amino and carboxyl terminal cysteine residues. The remaining peptide sequence found in the mimics is native to the C-C′ region of Fc RI R2.…”