N-Benzoyl amino acids as LFA-1/ICAM inhibitors 1: amino acid structure-activity relationship.
The association of ICAM-1 with LFA-1 plays a critical role in several autoimmune diseases. N-2-Bromobenzoyl L-tryptophan, compound 1, was identified as an inhibitor to the formation of the LFA-1/ICAM complex. The SAR of the amino acid indicates that the carboxylic acid is required for inhibition and that L-histidine is the most favored amino acid.
Burdick
Daniel J
DJ
Department of Bioorganic Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. burdick.dan@gene.com
Paris
Ken
K
Weese
Kenneth
K
Stanley
Mark
M
Beresini
Maureen
M
Clark
Kevin
K
McDowell
Robert S
RS
Marsters
James C
JC
Gadek
Thomas R
TR
D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006639:Histidine / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D002264:Carboxylic Acids; D007202:Indicators and Reagents; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D006639:Histidine