TY - JOUR
T1 - Matrix metalloproteinase inhibitors
T2 - A structure-activity study
AU - Levy, Daniel E.
AU - Lapierre, France
AU - Liang, Weisheng
AU - Ye, Wenqing
AU - Lange, Christopher W.
AU - Li, Xiaoyuan
AU - Grobelny, Damian
AU - Casabonne, Marie
AU - Tyrrell, David
AU - Holme, Kevin
AU - Nadzan, Alex
AU - Galardy, Richard E.
PY - 1998
Y1 - 1998
N2 - Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids inaddition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (2) Potent inhibitorsmust possess string zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustratedby itsability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.
AB - Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids inaddition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (2) Potent inhibitorsmust possess string zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustratedby itsability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.
UR - https://www.webofscience.com/wos/woscc/full-record/WOS:000071538200008
UR - https://openalex.org/W1980443285
UR - https://www.scopus.com/pages/publications/15444343493
U2 - 10.1021/jm970494j
DO - 10.1021/jm970494j
M3 - Journal Article
SN - 0022-2623
VL - 41
SP - 199
EP - 223
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 2
ER -