Backbone cyclization: A new method for conferring conformational constraint on peptides.
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.
Gilon
C
C
Department of Organic Chemistry, Hebrew University of Jerusalem, Israel.
Halle
D
D
Chorev
M
M
Selinger
Z
Z
Byk
G
G
D000595:Amino Acid Sequence; D003500:Cyclization; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013373:Substance P / Q000031:analogs & derivatives / Q000737:chemistry
D010446:Peptide Fragments; D010455:Peptides; D013373:Substance P; C054725:septide; D011761:Pyrrolidonecarboxylic Acid