I gained my PhD from the University of Nottingham in 1988 under the supervision of Professor Barrie Bycroft and Dr Ray Grout. This was followed by a period of postdoctoral training (1988-1992) under the guidance of Barrie Bycroft (Univ Nottingham), Gordon Roberts (Univ Leicester) and Mike Gasson (IFR, Norwich). In 1992, I was appointed to a lectureship at Nottingham, and was promoted to Senior Lecturer in 2000 and then to Reader in Chemical Biology in 2007.
Since 1992, I have supervised over 40 PhD and MRes students who have successfully defended their theses. Over the same period, I have mentored over 10 postdoctoral fellows. A significant milestone in my career was the publication of my authoritative book 'Fmoc Solid Phase Peptide Synthesis: A Practical Approach' in 2000, which soon became an international 'Peptide Chemist Bible'. In 2006, I organised and chaired the first Merck Biosciences/RSC-sponsored mini-symposium on 'Chemistry and Biology of Peptides'.
Over the last decade, I was instrumental in the development of a series of unique multi-functional/orthogonally protected chemical reagents, e.g. novel 4-azalysine analogues, which facilitated the construction of hybrid and complex peptides. The Dde-based chemistry and chemical toolkits, ranging from amine- (Bycroft et al 1993, 1994, Nash et al 1996) and carboxy-protecting groups (Chan et al 1995) to novel tagging reagents and pseudoaromatic amino acids (Middleton et al 2004), which are now widely used by the biomedical and chemical community, were discovered and further developed in my laboratory.
I am a Fellow of the Royal Society of Chemistry, and was recently (in 2009) a Visiting Professor at the Universite Pierre et Marie Curie, Paris, FRANCE. I am currently a member of the editorial board for the Journal of Chemical Biology.
Practical Pharmaceutical Chemistry; Bacterial & Fungal Infection; Research Project
My research activities are primarily hypothesis driven, and take a multidisciplinary but yet integrative approach to the identification, construction and manipulation of molecules to address defined… read more
My research activities are primarily hypothesis driven, and take a multidisciplinary but yet integrative approach to the identification, construction and manipulation of molecules to address defined biomedical objectives. A rational chemical design process is extensively applied for the production of novel macrocyclic peptides, peptidomimetics and low-molecular weight molecules.
These agents are used either as chemical tools to interrogate or to illuminate biomolecular interactions, or as lead drug candidates. The thematic areas in which this integrative chemical biology approach has been applied include: (i) Gram-positive pathogenicity; (ii) antimicrobials; and (iii) replication and translation systems.
I am one of the key drivers of the MRC Programme Grants (2003-08; 2009-2014; 2016-2020 with Paul Williams), which ensures delivery of vital molecules in the context of modern medicinal chemistry. My pivotal contribution focuses on the discovery of novel chemical agents that attenuates staphylococcal infection by inhibiting the expression of virulence proteome. Importantly, a thorough structure-activity relationship studies led to the hypothesis of a two-site binding model for the interaction of S. aureus cognate activating-ligand AIP with AgrC. This work has recently expanded to the molecular and structural studies of the AgrC receptor and the multi-functional bioprocessing enzyme AgrB, as well as studies directed towards other important pathogens such as Clostridium difficile.
Our recent minireview paper was highlighted as noteworthy in ChemistryViews http://www.chemistryviews.org/details/ezine/9535721/New_Antibiotics_Against_Resistant_Bacteria.html
Journal of Antimicrobial Chemotherapy Editor's Choice: 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a novel treatment for intravascular catheter infections due to Staphylococcus aureus
Membership of Professional Bodies & Committees
- Fellow of the Royal Society of Chemistry
- Committee member of the RSC Protein & Peptide Science Group
- Member of American Chemical Society
- Member of the American Peptide Society
- Member of the Society for Applied Microbiology