The design and synthesis of potent cyclic peptide VCAM-VLA-4 antagonists incorporating an achiral Asp-Pro mimetic

N Fotouhi; P Joshi; D Fry; C Cook; J W Tilley; G Kaplan; A Hanglow; K Rowan; V Schwinge; B Wolitzky

doi:10.1016/s0960-894x(00)00174-8

The design and synthesis of potent cyclic peptide VCAM-VLA-4 antagonists incorporating an achiral Asp-Pro mimetic

Bioorg Med Chem Lett. 2000 Jun 5;10(11):1171-3. doi: 10.1016/s0960-894x(00)00174-8.

Authors

N Fotouhi¹, P Joshi, D Fry, C Cook, J W Tilley, G Kaplan, A Hanglow, K Rowan, V Schwinge, B Wolitzky

Affiliation

¹ Roche Research Center, Hoffmann-La Roche Inc, Nutley, NJ 07110, USA. nader.fotouhi@roche.com

PMID: 10866374
DOI: 10.1016/s0960-894x(00)00174-8

Abstract

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.

MeSH terms

Aspartic Acid / chemistry*
Drug Design
Integrin alpha4beta1
Integrins / antagonists & inhibitors*
Molecular Mimicry
Peptides, Cyclic / chemical synthesis*
Peptides, Cyclic / chemistry
Peptides, Cyclic / pharmacology*
Proline / chemistry*
Receptors, Lymphocyte Homing / antagonists & inhibitors*
Vascular Cell Adhesion Molecule-1 / drug effects*

Substances

Integrin alpha4beta1
Integrins
Peptides, Cyclic
Receptors, Lymphocyte Homing
Vascular Cell Adhesion Molecule-1
Aspartic Acid
Proline