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James Redman

Dr James Redman

Senior Lecturer in Chemical Biology

School of Chemistry

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Overview

Dr Redman's research interests are in the areas of amino acid, protein and peptide chemistry, nucleic acids and mass spectrometry.
This work involves the synthesis of amino acids with heterocyclic side chains designed as building blocks for nucleic acid-binding peptides. We are preparing amino acids with mono- and bicyclic guanidine side chains as constrained analogues of arginine that are predicted to form hydrogen bonded interactions with nucleobases. Peptides can also be constrained by backbone cyclisation and we are investigating the use of computer aided interpretation of collision induced dissociation mass spectra of cyclic peptides as a tool for characterisation of this class of compound. A further project involves using phage display techniques to select allosteric DNA binding proteins, with the goal of creating artificial transcription factors that can be switched using a small molecule drug.

Links

Personal Web Site: James Redman

Publication

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Articles

Research

  • Protein engineering using phage display
  • Development of synthetic small molecule ligands for folded nucleic acids
  • Design of assays for probing interactions of ligands with nucleic acids
  • Computer assisted mass spectrometric structure determination of combinatorial library products
  • Application of solid phase chemistry for preparation of topologically diverse compounds

An understanding of the forces between molecules enables us to design synthetic compounds that interact with biological targets and to redesign natural biomolecules to achieve new functions. One of our research interests concerns the engineering of small molecule binding sites within proteins and in this area we are using phage display techniques to select for allosteric drug binding sites in zinc-finger transcription factor proteins.

Nucleic acids, and especially RNA, can adopt complex folded structures comparable to proteins and we are involved with development of small molecule ligands against these macromolecular targets. In order to realize our designs we need to call upon the skills of synthetic organic chemistry for preparation and assembly of molecular building blocks. We are currently synthesising a range of amino acids with guanidine side chains as building blocks for nucleic acid binding peptides.

One of our goals is to increase the efficiency with which we discover new ligands through a combination of miniaturized parallel synthesis and analysis to verify the identity of reaction products. We have a particular interest in the application of tandem mass spectrometry and computer assisted structure determination of peptides with unnatural topologies, including cyclic, branched and cross linked molecules. We are developing software for structure determination of these compounds using an automated analysis of fragmentation patterns. These classes of compound are amenable to parallel synthesis, and through a judicious choice of building blocks we can tune them to exhibit a desired biological activity such as selective recognition of a nucleic acid fold.

Teaching

CH0003 Chemistry of Organic Compounds

CH3216 Chemical Biology II: Introduction to Enzyme and Nucleic Acid Chemistry

CH3217 Biomolecular Chemistry

CH2317 Chemical Biology III: Biosynthetic Approach to Natural Products

CH3405 Organic Chemistry 2

CHT224 Medicinal Chemistry

CHT207 Biosynthetic Approach to Natural Products

CHT232 Key Skills for Postgraduate Chemists

Details of modules can be found in course finder.

Biography

PhD University of Cambridge (2000, J. K. M. Sanders, self-assembly of porphyrins). Wellcome Trust Travelling Research Fellowship (2000-3). Research Fellow, Scripps Research Institute (2000-2, M. R. Ghadiri, protein design and mass spectrometry of cyclic peptides). Research Associate, University of Cambridge (2002-6, S. Balasubramanian, recognition of guanine quadruplexes by proteins and small molecules). Appointed as Lecturer, Cardiff, in 2006.