ABSTRACT
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.
Subject(s)
Cysteine/chemistry , Integrins/antagonists & inhibitors , Receptors, Lymphocyte Homing/antagonists & inhibitors , Cysteine/pharmacology , Integrin alpha4beta1 , Interleukin-8/pharmacology , Protein Binding , Structure-Activity Relationship , Vascular Cell Adhesion Molecule-1/metabolismABSTRACT
Using disulphide cysteine-based inhibitors as lead structures, this communication describes our strategy for identifying more stable, potent antagonists of the alpha4beta1 integrin. These studies ultimately discovered potent, low molecular weight inhibitors based on D-thioproline-L-tyrosine.
Subject(s)
Integrins/antagonists & inhibitors , Receptors, Lymphocyte Homing/antagonists & inhibitors , Tyrosine/chemistry , Animals , Bronchial Hyperreactivity/drug therapy , Half-Life , Integrin alpha4beta1 , Interleukin-8/pharmacology , Methacholine Chloride/pharmacology , Parasympathomimetics/pharmacology , Protein Binding , Rats , Sheep , Structure-Activity Relationship , Tyrosine/pharmacokinetics , Tyrosine/pharmacology , Vascular Cell Adhesion Molecule-1/metabolismABSTRACT
Five Giardia stocks collected from animals and man in Alberta, Canada, were compared by DNA fingerprinting. Although many DNA bands were common to all stocks, differences in the DNA banding patterns were seen. These same stocks had previously been shown to be identical by restriction enzyme cleavage of genomic DNA.
