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Synthesis and enzymatic evaluation of a P1 arginine aminocoumarin substrate library for trypsin-like serine proteases
P D Edwards1, R C Mauger, K M Cottrell
1Department of Chemistry, AstraZeneca Pharmaceuticals, Wilmington, DE 19850-5437, USA. philip.edwards@astrazeneca.com
Abstract:
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.
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