Proteases target

A sutfonylating agent (abbreviated PMSE) that irreversibly inhibits many serine esterases and serine proteases . Target enzymes usually react with PMSE and related alkylating agents through the activated imidazole group of a histidyl residue that is part of the catalytic triad. 

It has been known for some time that many examples of naturally occurring Kunitz inhibitors exist, both isolated and as domains in larger proteins, which inhibit a variety of serine proteases [47]. This strongly suggests that this molecular framework is compatible with inhibition of this general class. The contact region between these inhibitors and their protease targets is known from a... 

Receptor targets. Protease targets SignaHransduction protein-targets... 

Protease-targeted peptidomimetics derived by ligand structure-based drug... 

Protease structure-based drug design HIV protease-targeted peptidomimetics and nonpeptides... 

Lang, S.A., Kozyukov, A.V., Balakin, K.V., Skorenko, A.V., Ivashchenko, A.A. and Savchuk, N.P. (2002) Classification scheme for the design of serine protease targeted compound libraries. J Comput Aided Mol Design, 16, 803-807. 

By the end of 2002, the Aventis project portfolio was transformed. Of the 139 projects in the LI phase, the kinase and GPCR target families each contributed 19%, the protease and ion channels/transporters about 8% each. For projects in the candidate identification phase, GPCR, kinase, and protease target families each contributed about 20% of the compounds and ion channels/transporters about 12% of the compounds in the portfolio. 

Internally quenched fluorogenic substrate probes have been shown to be useful in a variety of contexts, from conventional enzymology and inhibitor evaluation, to searches for important new therapeutic protease targets. The development of automated methods for synthesis of these substrate probes has enabled access to a wide range of substrate sequences, and facilitated detailed studies of enzyme-substrate sub-site interactions. The selection of the Edans-Dabcyl fLuorophore-quencher pair has led to the synthesis of efficiently quenched peptide substrates containing more than 30 amino add residues. The overall versat bty of these substrate probes ensures widespread future application to studies of many new and existing proteases of interest. 

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