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- Title
Development of 6′-N-Acylated Isepamicin Analogs with Improved Antibacterial Activity against Isepamicin-Resistant Pathogens.
- Authors
Ban, Yeon Hee; Song, Myoung Chong; Kim, Hee Jin; Lee, Heejeong; Wi, Jae Bok; Park, Je Won; Lee, Dong Gun; Yoon, Yeo Joon
- Abstract
The development of new aminoglycoside (AG) antibiotics has been required to overcome the resistance mechanism of AG-modifying enzymes (AMEs) of AG-resistant pathogens. The AG acetyltransferase, AAC(6′)-APH(2″), one of the most typical AMEs, exhibiting substrate promiscuity towards a variety of AGs and acyl-CoAs, was employed to enzymatically synthesize new 6′-N-acylated isepamicin (ISP) analogs, 6′-N-acetyl/-propionyl/-malonyl ISPs. They were all active against the ISP-resistant Gram-negative bacteria tested, and the 6′-N-acetyl ISP displayed reduced toxicity compared to ISP in vitro. This study demonstrated the importance of the modification of the 6′-amino group in circumventing AG-resistance and the potential of regioselective enzymatic modification of AG scaffolds for the development of more robust AG antibiotics.
- Subjects
AMES (Iowa); GRAM-negative bacteria; PATHOGENIC microorganisms; ACETYLTRANSFERASES; ACYLTRANSFERASES; ANTIBIOTICS
- Publication
Biomolecules (2218-273X), 2020, Vol 10, Issue 6, p893
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom10060893