Molecular modeling and computer-aided design of potential protease inhibitors

Keywords

Molecules -- Models, Protease inhibitors, Serine proteinases -- Inhibitors, Trypsin inhibitors, Phenylthiohydantoin-arginine, Molecular docking, Structure-based drug design, Hydrophobic tetrapeptide-hydrophilic dipeptide hybrids, Fluorescence assay (bovine trypsin inhibition)

Abstract

The mode of action of known natu,ral and syritheti�� inhibitors of the serine _ protease trypsin was studied using struc��e-based drug design: Three groups of putative . . inhibitors were examined. Group I inhibitors consist of molecules designed to incorporate the binding properties of a natural inhibit��r. Group 11 inhibitors wern . . . constructed from a combination of a· hydrophobic tetrapeptide and a hydrophilic di peptide, and Group III were cyclic phenylthiohydru1toin deriv��tives: As a result of the study of the interactioris between certain residri���� or.features of the inhibitor m��lecule,

such as hydrophobic appendages . or cyclic conformation, .. and specific .· binding sites . on the surface of the enzyme, the_ ma1n features of binding of the serine proteases were delineated Relative binding eilergi��s obtained fr��m moJecular modeling and computational chemistry show that _many of th_e de��igned 1nhibitors exhibit fav9rable . binding. One lead compound, a phenylthiohydantoin- arginine • was shown ��y fluoresc��nt _­ assay.to inhibit Bovine trypsin.

Notes

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Graduation Date

1999

Semester

Summer

Advisor

Price, Harry

Degree

Master of Science (M.S.)

College

College of Arts and Sciences

Department

Chemistry

Format

PDF

Pages

66 pages

Language

English

Length of Campus-only Access

None

Access Status

Masters Thesis (Open Access)

Identifier

DP0028704

Subjects

Arts and Sciences -- Dissertations; Academic; Dissertations; Academic -- Arts and Sciences; Trypsin inhibitors; Serine proteinases--Inhibitors; Drugs--Design--Computer simulation; Drugs--Structure-activity relationships--Computer simulation; Ligand binding (Biochemistry)--Computer simulation

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