Journal of Medicinal Chemistry 1992-10-16

A general method for the preparation of internally quenched fluorogenic protease substrates using solid-phase peptide synthesis.

L L Maggiora, C W Smith, Z Y Zhang

Index: J. Med. Chem. 35 , 3727, (1992)

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Abstract

A general scheme for obtaining a fluorescent donor/acceptor peptide substrate via solid-phase synthesis methodology is presented. The key feature of this method is the design of a glutamic acid derivative that has been modified on the carboxyl side chain with a 5-[(2'-aminoethyl)-amino]naphthelenesulfonic acid (EDANS) to create a fluorescent donor moiety that can be incorporated near the C-terminus of the peptide substrate. The corresponding fluorescent acceptor group containing a 4-[[4-(dimethylamino)phenyl]azo]benzoic acid (DABCYL) can then be attached to the resin-bound peptide at the N-terminus while all side-chain groups are still fully protected. Substrates for renin and HIV proteinase are synthesized as examples.