Melinda G. Axel

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The proteolytic enzyme stromelysin-1 is a member of the family of matrix metalloproteinases and is believed to play a role in pathological conditions such as arthritis and tumor invasion. Stromelysin-1 is synthesized as a pro-enzyme that is activated by removal of an N-terminal prodomain. The active enzyme contains a catalytic domain and a C-terminal(More)
Carboxyalkyl peptides containing a biphenylylethyl group at the P1' position were found to be potent inhibitors of stromelysin-1 (MMP-3) and gelatinase A (MMP-2), in the range of 10-50 nM, but poor inhibitors of collagenase (MMP-1). Combination of a biphenylylethyl moiety at P1', a tert-butyl group at P2', and a methyl group at P3' produced orally(More)
Pharmaceutical companies spend billions of dollars annually on drug discovery research. In the process, they generate vast amounts of scientific data. Data warehousing could significantly shorten the research cycle that leads to a new drug. We propose a framework for the application of data warehousing to integrate a pharmaceutical company’s drug discovery(More)
Stromelysin-1 is a matrix metalloprotease that has been implicated in a number of degenerative diseases. Here we present the refined NMR solution structure of the catalytic domain of stromelysin-1 complexed with a small inhibitor and compare it to the X-ray crystal structure of the same complex. The structures are similar in global fold and show an unusual(More)
Design and synthesis of nonpeptidal bis-tetrahydrofuran ligands based upon the X-ray crystal structure of the HIV-1 protease-inhibitor complex 1 led to replacement of two amide bonds and a 10 pi-aromatic system of Ro 31-8959 class of HIV protease inhibitors. Detailed structure-activity studies have now established that the position of ring oxygens, ring(More)
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