Discovery and evaluation of potent, cysteine-based alpha4beta1 integrin antagonists.
Acyclic, disulphide derivatives of cysteine have been identified as moderately potent antagonists of alpha4beta1-mediated leukocyte cell adhesion to VCAM. This communication describes how they were discovered from a simple L-cystine derivative and using the structure-activity data of C*DThioPC* related cyclic peptides.
Archibald
S C
SC
Celltech Chiroscience, Slough, UK.
Head
J C
JC
Linsley
J M
JM
Porter
J R
JR
Robinson
M K
MK
Shock
A
A
Warrellow
G J
GJ
D003545:Cysteine / Q000737:chemistry* / Q000494:pharmacology; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors*; D016209:Interleukin-8 / Q000494:pharmacology; D011485:Protein Binding; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D039041:Integrin alpha4beta1; D016023:Integrins; D016209:Interleukin-8; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D003545:Cysteine