Backbone cyclization: A new method for conferring conformational constraint on peptides
- 1 May 1991
- journal article
- research article
- Published by Wiley in Biopolymers
- Vol. 31 (6), 745-750
- https://doi.org/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 ω-substituted alkylidene chains replacing Nα or Cα 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.Keywords
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