Backbone cyclization: A new method for conferring conformational constraint on peptides

Biopolymers. 1991 May;31(6):745-50. doi: 10.1002/bip.360310619.

Abstract

This article describes a new concept of medium- and long-range cyclization of peptides through "backbone cyclization." In this approach, conformational constraints are conferred on a peptide by linking omega-substituted alkylidene chains replacing N(alpha) or C(alpha) hydrogens in a peptidic backbone. Backbone cyclization, which is divided into N-backbone and C-backbone cyclizations, allow for new modes of cyclization in addition to the classical ones that are limited to cyclization through the side chains and/or the amino or carboxyl terminal groups. The article also describes the application of the N-backbone cyclization to the active region of substance P. Conformational constraints of this peptide by the classical cyclization modes led to inactive analogues whereas N-backbone cyclization provided an active, selective, and metabolically stable analogue.

MeSH terms

  • Amino Acid Sequence
  • Cyclization
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptides / chemistry*
  • Protein Conformation*
  • Pyrrolidonecarboxylic Acid / analogs & derivatives
  • Substance P / analogs & derivatives
  • Substance P / chemistry

Substances

  • Peptide Fragments
  • Peptides
  • Substance P
  • septide
  • Pyrrolidonecarboxylic Acid