Synthesis and enzymatic evaluation of a P-1 arginine aminocoumarin substrate library for trypsin-like serine proteases

A method for the solid-phase synthesis of P-1 arginine containing peptides via attachment of the arginine side-chain guanidine group is described. Thi s procedure is applied to the preparation of a tetrapeptide, P-1 arginine a minocoumarin PS-SCL. This library was validated by using it to determine th e P-4-P-2 specificity for thrombin and comparing the results to the known t hrombin subsite specificity. This is the first reported example of a PS-SCL library containing a P-1 arginine. (C) 2000 Elsevier Science Ltd. All righ ts reserved.