Conformational studies on model dipeptides of Gly, L-Ala and their C alpha-substituted analogs.
As a part of the development of conformational guidelines for the design of metabolically altered peptidomimetics, we present conformational energy calculations on model dipeptide compounds with glycine (Gly), L-alanine (Ala), alpha-aminoisobutyric acid (Aib), L-tert-butylglycine (Tle), L-phenylglycine (Phg), (alpha, alpha)-diphenylglycine (D phi g), L-2-aminobutyric acid (Abu), 2-amino-2-ethylbutyric acid (Deg), L-2-amino-2-vinylacetic acid (Ava) and (alpha, alpha)-divinylglycine (Dvg). The energy calculations have been made using molecular mechanics methods with a force field derived from MM2. The salient features are expressed in terms of conformational energy plots, drawn as a function of the backbone torsion angles phi(Ci'-1-Ni-Ci alpha i-Ci') and psi(Ni-Ci alpha -C'-N(i+1)). The low-energy structures of these compounds are qualitatively consistent with the X-ray crystal structure analyses of peptides and peptidomimetics. They are also in agreement with the results of the solution-phase studies carried out by NMR and IR techniques. The results obtained have important implications in the design of conformationally restricted peptidomimetics.
Ramnarayan
K
K
ImmunoPharmaceutics Inc., San Diego, California, USA.
Chan
M F
MF
Balaji
V N
VN
Profeta
S
S
Rao
S N
SN
D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry*; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D004151:Dipeptides; D000409:Alanine; D005998:Glycine