skip to content

Yusuf Hamied Department of Chemistry

Portrait of fjl1

Coenzyme Chemistry

Thiamin diphosphate (TPP) 1 is a coenzyme used by many enzymes which make and break bonds adjacent to keto groups. We have synthesised deaza analogues (e.g. 2) of intermediates in these reactions. These bind extremely tightly to TPP-dependent enzymes. We aim to make further analogues that are inhibitors of specific enzymes and may thus be of medicinal importance. We also hope to get crystal structures of the analogues bound to their target enzymes which should help to understand how the reactions occur.

Novel Catalysts

Thiazolium salts catalyse a variety of reactions involving making and breaking bonds to a carbonyl carbon (e.g. the benzoin condensation). We have made chiral thiazolium salts (e.g. 3) and have observed asymmetric induction in formation of benzoin. We intend to further develop these catalysts to obtain better levels of asymmetric induction, to probe the mechanism and to introduce binding cavities for increased rate and better selectivities.

Enzyme Chemistry

A key step in tetrapyrrole biosynthesis is the linking of four molecules of the monopyrrole PBG (4) to give a linear tetrapyrrole, catalysed by PBG deaminase. A crystal structure is available and we plan to use this to design and then synthesise analogues of PBG which bind tightly to the enzyme. These will aid understanding of the mechanism and may be of value as antibiotics and/or herbicides.

Biosynthesis of Prodigiosin

(with Prof G. Salmond, Biochemistry) Prodigiosin (see below) is an immunosuppressant with a novel mode of action. We have found the cluster of genes that codes for its biosynthesis in Serratia marcescens and are working on the elucidation of the biosynthetic pathway and the mechanisms of the enzymic reactions involved.

Synthetic Methods for PET

(with Dr F. Aigbirhio, Wolfson Brain Imaging Centre) Positron Emission Tomography (PET) is a technique used for scanning human brain to detect the distribution of compounds of diagnostic interest. It relies on compounds labelled with very short- lived radioisotopes (e.g. 11C or 18F). The whole synthesis of such compounds must not take longer than ~30 mins. The aim of this project is to develop new synthetic methods, using polymer-supported reagents, that will allow such rapid synthesis and isolation of labelled compounds of neuropharmacological importance.

Dr Leeper discusses his research


Synthesis of pyrrothiamine, a novel thiamine analogue, and evaluation of derivatives as potent and selective inhibitors of pyruvate dehydrogenase.
FJ Leeper, AHY Chan, TCS Ho, K Agyei-Owusu
– Organic & biomolecular chemistry
Enzyme-Catalyzed Spiroacetal Formation in Polyketide Antibiotic Biosynthesis.
O Bilyk, GS Oliveira, RM de Angelo, MO Almeida, KM Honório, FJ Leeper, MVB Dias, PF Leadlay
– Journal of the American Chemical Society
Metabolic Glycan Labelling of Cancer Cells using Variably Acetylated Monosaccharides
DR Parle, F Bulat, S Fouad, H Zecchini, KM Brindle, AA Neves, FJ Leeper
– Bioconjug Chem
Thiamine analogues as inhibitors of pyruvate dehydrogenase and discovery of a thiamine analogue with non-thiamine related antiplasmodial activity
AHY Chan, I Fathoni, TCS Ho, KJ Saliba, FJ Leeper
– RSC Medicinal Chemistry
Prodrugs of pyrophosphates and bisphosphonates: disguising phosphorus oxyanions
FJ Leeper, ES Rudge, AHY Chan
– RSC medicinal chemistry
Mechanistic Insights into Dideoxygenation in Gentamicin Biosynthesis
S Li, PD Santos Bury, F Huang, J Guo, G Sun, A Reva, C Huang, X Jian, Y Li, J Zhou, Z Deng, FJ Leeper, PF Leadlay, MVB Dias, Y Sun
– ACS Catalysis
Chris Abell 1957–2020
FJ Leeper, AG Coyne
– The Biochemist
Revision in the first steps of the biosynthesis of the red antibiotic prodigiosin: use of a synthetic thioester to validate a new intermediate.
M Couturier, HD Bhalara, RE Monson, GPC Salmond, FJ Leeper
– RSC Chem Biol
18F-C2Am: a targeted imaging agent for detecting tumor cell death in vivo using positron emission tomography
F Bulat, F Hesse, D-E Hu, S Ros, W-H Connor, B Xie, B Attili, D Soloviev, F Aigbirhio, F Leeper, K Brindle, A Neves
– EJNMMI Research
Development of targeted imaging agents for detecting tumour cell death
F Bulat, A Neves, F Hesse, D-E Hu, F Aigbirhio, F Leeper, K Brindle
  • 1 of 18
  • >

Research Groups

Research Interest Groups

Telephone number

01223 336403

Email address