N-Aryl sulfonyl homocysteine hydroxamate inhibitors of matrix metalloproteinases: further probing of the S(1), S(1)', and S(2)' pockets.
A series of N-arylsulfonyl S-alkyl homocysteine hydroxamic acids were synthesized with variations in three subsites corresponding to P(1), P(1)', and P(2)'. Enzyme assays with a variety of MMPs revealed activity at the low nanomolar level.
Hanessian
S
S
Department of Chemistry, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Québec H3C 3J7, Canada. stephen.hanessisan@umontreal.ca
Moitessier
N
N
Gauchet
C
C
Viau
M
M
D017364:Collagenases / Q000737:chemistry; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D020781:Matrix Metalloproteinase 1 / Q000737:chemistry; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship
D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D006710:Homocysteine; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1