Related Experiment Video
Updated: May 21, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
HIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid Biosynthesis
Yonghui Zhang1, Fu-Yang Lin, Kai Li
1PrenylX Research Institute, Zhangjiagang, 215600, P.R. China.
None:
We report the discovery of antibacterial leads, keto- and diketo-acids, targeting two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and dehydrosqualene synthase (CrtM). The leads were suggested by the observation that keto- and diketo-acids bind to the active site Mg(2+)/Asp domain in HIV-1 integrase, and similar domains are present in prenyl transferases. We report the x-ray crystallographic structures of one diketo-acid and one keto-acid bound to CrtM, which supports the Mg(2+) binding hypothesis, together with the x-ray structure of one diketo-acid bound to UPPS. In all cases, the inhibitors bind to a farnesyl diphosphate substrate-binding site. Compound 45 had cell growth inhibition MIC(90) values of ~250-500 ng/mL against S. aureus, 500 ng/mL against Bacillus anthracis, 4 microg/mL against Listeria monocytogenes and Enterococcus faecium, and 1 microg/mL against Streptococcus pyogenes M1, but very little activity against E. coli (DH5α, K12) or human cell lines.
Related Concept Videos
Inhibitors of Bacterial Protein Synthesis
Inhibitors of Viral Protein Synthesis
Inhibitors of Bacterial DNA Synthesis
Inhibitors of Gram-positive Cell Wall Synthesis
Antibiotic Selection
Retrovirus Life Cycles

