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Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors.
- Source :
-
The Journal of antibiotics [J Antibiot (Tokyo)] 2019 Jun; Vol. 72 (6), pp. 325-349. Date of Electronic Publication: 2019 Apr 15. - Publication Year :
- 2019
-
Abstract
- Adenylate-forming enzymes are a mechanistic superfamily that are involved in diverse biochemical pathways. They catalyze ATP-dependent activation of carboxylic acid substrates as reactive acyl adenylate (acyl-AMP) intermediates and subsequent coupling to various nucleophiles to generate ester, thioester, and amide products. Inspired by natural products, acyl sulfonyladenosines (acyl-AMS) that mimic the tightly bound acyl-AMP reaction intermediates have been developed as potent inhibitors of adenylate-forming enzymes. This simple yet powerful inhibitor design platform has provided a wide range of biological probes as well as several therapeutic lead compounds. Herein, we provide an overview of the nine structural classes of adenylate-forming enzymes and examples of acyl-AMS inhibitors that have been developed for each.
Details
- Language :
- English
- ISSN :
- 1881-1469
- Volume :
- 72
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of antibiotics
- Publication Type :
- Academic Journal
- Accession number :
- 30982830
- Full Text :
- https://doi.org/10.1038/s41429-019-0171-2