Research Sample

Research Sample
About Robin
Positions vacant
To give a flavour of the work carried out in my group, the following pages provide a simplified summary of a recent piece of research to use combinatorial peptide libraries in order to select tight-binding inhibitors of serine proteases. Full details can be found in the following reference:
McBride, J.D., Freeman, N., Domingo, G.J. and Leatherbarrow, R.J. (1996) Selection of chymotrypsin inhibitors from a conformationally-constrained combinatorial library. J. Mol. Biol. 259, 819-827. PDF_icon.gif (303 bytes) 557KB

Aims of this Research

Protease inhibitors have great potential therapeutic importance, and many such inhibitors are used in the pharmaceutical industry. Their applications include anti-coagulants, anti-inflammatory and anti-viral agents. There is great interest both in development of new inhibitors of this class, and in understanding the basic processes of protease inhibition. This present work, which is funded by GlaxoSmithKline, had the following immediate aims:

Peptide Library

  1. To use an immobilised peptide template that retains the binding motif from a macromolecular protease inhibitor protein.
  2. To introduce combinatorial variation in the region that is responsible for binding specificity. The form of library to be used is a "one bead, one peptide" library.
  3. To screen this library for binding to selected serine protease enzymes
  4. To identify