The design and synthesis of potent cyclic peptide VCAM-VLA-4 antagonists incorporating an achiral Asp-Pro mimetic.
The Asp-Pro sequence of the cyclic peptide Ac-HN-Tyr-Cys*-Asp-Pro-Cys*-OH (1) could be replaced with the achiral dipeptide mimetic 1-(2-aminoethyl)cyclpentylcarboxylic acid with retention of potent inhibition of the VCAM-VLA-4 interaction.
Fotouhi
N
N
Roche Research Center, Hoffmann-La Roche Inc, Nutley, NJ 07110, USA. nader.fotouhi@roche.com
Joshi
P
P
Fry
D
D
Cook
C
C
Tilley
J W
JW
Kaplan
G
G
Hanglow
A
A
Rowan
K
K
Schwinge
V
V
Wolitzky
B
B
D001224:Aspartic Acid / Q000737:chemistry*; D015195:Drug Design; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors*; D018716:Molecular Mimicry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011392:Proline / Q000737:chemistry*; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors*; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects*
D039041:Integrin alpha4beta1; D016023:Integrins; D010456:Peptides, Cyclic; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D001224:Aspartic Acid; D011392:Proline