Projects per year
There is an urgent need for the development of new therapeutics with novel modes of action to target Gram-negative bacterial infections, due to resistance to current drugs. Previously, FabA, an enzyme in the bacterial type II fatty acid biosynthesis pathway, was identified as a potential drug target in Pseudomonas aeruginosa, a Gram-negative bacteria of significant clinical concern. A chemical starting point was also identified. There is a cysteine, Cys15, in the active site of FabA, adjacent to where this compound binds. This paper describes the preparation of analogues containing an electrophilic warhead with the aim of covalent inhibition of the target. A wide variety of analogues were successfully prepared. Unfortunately, these analogues did not increase inhibition, which may be due to a loop within the enzyme partially occluding access to the cysteine.
|Number of pages||18|
|Early online date||27 Mar 2023|
|Publication status||Published - 11 Apr 2023|
- Organic compounds
- Peptides and proteins
ASJC Scopus subject areas
- Chemical Engineering(all)
FingerprintDive into the research topics of 'Design and synthesis of covalent inhibitors of FabA'. Together they form a unique fingerprint.
- 1 Active
Wellcome Centre for Anti-Infectives Research
Cook, S., De Rycker, M., Fairlamb, A., Ferguson, M., Field, M., Gilbert, I., Gray, D., Horn, D., Pawlowic, M., Read, K., Wyatt, P. & Wyllie, S.
1/04/17 → 31/03/24