Rapid assembly of matrix metalloprotease inhibitors using click chemistry.
[reaction: see text] A panel of 96 metalloprotease inhibitors was assembled using "click chemistry" by reacting eight zinc-binding hydroxamate warheads with 12 azide building blocks. Screens of the bidentate compounds against representative metalloproteases provided discerning inhibition fingerprints, revealing compounds with low micromolar potency against MMP-7. The relative ease and convenience of the strategy in constructing focused chemical libraries for rapid in situ screening of MMPs is thereby demonstrated.
Wang
Jun
J
Department of Chemistry, Medicinal Chemistry Program of the Office of Life Sciences, National University of Singapore, 3 Science Drive 3, Singapore 117543, Republic of Singapore.
Uttamchandani
Mahesh
M
Li
Junqi
J
Hu
Mingyu
M
Yao
Shao Q
SQ
D001407:Bacillus / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors