Synthesis of an inhibitor-tethered resin for detection of active matrix metalloproteinases involved in disease.
Matrix metalloproteinases (MMPs), of which 26 members are known in humans, are implicated in a number of diseases. Their activity is strictly controlled, but when the biological control over the activity is lost, disease processes set in. In an attempt to delineate what MMP activity has gone awry in what diseases, including metastatic cancers that are of special interest to our laboratories, we conceived and synthesized two chromatographic resins incorporated with a multifunctional broad-spectrum inhibitor for MMPs. The broad-spectrum inhibitor contains three sterogentic centers and was synthesized in 13 steps. Two structural variants of the inhibitors were linked to the polymer support via disulfide moieties. These resins are intended for use in cellular systems to selectively fish out from a complex mixture of all cellular proteins the active MMP forms important for the specific disease for identification.
Hesek
Dusan
D
Department of Chemistry and Biochemistry and the Walther Cancer Research Center, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Toth
Marta
M
Krchnak
Viktor
V
Fridman
Rafael
R
Mobashery
Shahriar
S
D004194:Disease; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases