Synthesis and enzymatic evaluation of a P1 arginine aminocoumarin substrate library for trypsin-like serine proteases

• Published in: Bioorganic & medicinal chemistry letters Vol. 10; no. 20; pp. 2291 - 2294
• Main Authors: EDWARDS, Philip D, MAUGER, Russell C, COTTRELL, Kevin M, MORRIS, Frank X, PINE, Kara K, SYLVESTER, Mark A, SCOTT, Clay W, FURLONG, Stephen T
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 16-10-2000
• Subjects: Analytical, structural and metabolic biochemistry; Arginine; Biological and medical sciences; Coumarins; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Hydrolases; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - metabolism; Peptide Library; Protein Conformation; Serine Endopeptidases - metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure-Activity Relationship; Substrate Specificity; Thrombin - metabolism; Trypsin - metabolism; Human; Peptide library; Serine endopeptidases; Peptides; Enzyme; Coumarine derivatives; Combinatorial chemistry; Thrombin; In vitro; Substrate; Peptidases; Structure activity relation; Tetrapeptide; Substrate specificity; Chemical compound library; Hydrolases; Peptide synthesis; Solid phase; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/s0960-894x(00)00460-1

A method for the solid-phase synthesis of P1 arginine containing peptides via attachment of the arginine side-chain guanidine group is described. This procedure is applied to the preparation of a tetrapeptide, P1 arginine aminocoumarin PS-SCL. This library was validated by using it to determine the P4-P2 specificity for thrombin and comparing the results to the known thrombin subsite specificity. This is the first reported example of a PS-SCL library containing a P1 arginine.