A compendium of compounds designed as dipeptide mimetics was collected
from the literature. Conformational space available to these molecule
s was evaluated to obtain distance and torsion angle parameters to aid
in selection of mimetics for specific target peptides or to explore d
iversity strategies. Conformations were searched using the RandomSearc
h algorithm in SYBYL. Data were collected for conformations of each mo
lecule falling within 5 kcal/mol of the minimum. The distance between
capping groups on the N- and C-termini of the molecules was measured a
s well as the pseudotorsion angle about a virtual bond between these t
wo points. Molecules are classified based on the torsion angle space o
ccupied and range of distances spanned by the resulting conformations.
A large percentage of the dipeptide mimetics studies here have redund
ant conformational properties. The distribution of distances for all m
olecules covers an overall range of 3-15 Angstrom, the majority fallin
g between 5-8 Angstrom. The angles for the majority of the molecules c
over a wide range of torsional space with essentially no gaps in the v
alues they can occupy, although these molecules can be subdivided by t
he average distance spanned by the allowed conformations. A smaller gr
oup of molecules have torsion angles that are restricted to a range of
+/-60 degrees about the cis position (0 degrees). Representative exam
ples of each group are shown. We conclude that despite the significant
effort to devise unique molecular structures as dipeptide mimetics, t
here is a need for more conformationally restricted compounds to mimic
specific peptide conformations, and to complement molecular diversity
strategies. (C) 1997 John Wiley & Sons, Inc.