1312471-06-9Relevant academic research and scientific papers
Synthesis and Biological Activity of Mono- and Di-N-acylated Aminoglycosides
Chandrika, Nishad Thamban,Green, Keith D.,Houghton, Jacob L.,Garneau-Tsodikova, Sylvie
supporting information, p. 1134 - 1139 (2015/11/24)
Despite issues with oto/nephrotoxicity and bacterial resistance, aminoglycosides (AGs) remain an effective and widely used class of antibacterial agents. For decades now, efforts toward the development of novel AGs with potential to overcome some of these
Assessment of 6′- and 6′′′-N-acylation of aminoglycosides as a strategy to overcome bacterial resistance
Shaul, Pazit,Green, Keith D.,Rutenberg, Roi,Kramer, Maria,Berkov-Zrihen, Yifat,Breiner-Goldstein, Elinor,Garneau-Tsodikova, Sylvie,Fridman, Micha
, p. 4057 - 4063 (2011/06/28)
Amongst the many synthetic aminoglycoside analogues that were developed to regain the efficacy of this class of antibiotics against resistant bacterial strains, the 1-N-acylated analogues are the most clinically used. In this study we demonstrate that 6′-
Exploring the substrate promiscuity of drug-modifying enzymes for the chemoenzymatic generation of N-acylated aminoglycosides
Green, Keith D.,Chen, Wenjing,Houghton, Jacob L.,Fridman, Micha,Garneau-Tsodikova, Sylvie
scheme or table, p. 119 - 126 (2010/11/18)
Aminoglycosides are broad-spectrum antibiotics commonly used for the treatment of serious bacterial infections. Decades of clinical use have led to the widespread emergence of bacterial resistance to this family of drugs limiting their efficacy in the clinic. Here, we report the development of a methodology that utilizes aminoglycoside acetyltransferases (AACs) and unnatural acyl coenzyme A analogues for the chemoenzymatic generation of N-acylated aminoglycoside analogues. Generation of N-acylated aminoglycosides is followed by a simple qualitative test to assess their potency as potential antibacterials. The studied AACs (AAC(6′)-APH(2″) and AAC(3)-IV) show diverse substrate promiscuity towards a variety of aminoglycosides as well as acyl coenzyme A derivatives. The enzymes were also used for the sequential generation of homo- and hetero-di-N-acylated aminoglycosides. Following the clinical success of the N-acylated amikacin and arbekacin, our chemoenzymatic approach offers access to regioselectively N-acylated aminoglycosides in quantities that allow testing of the antibacterial potential of the synthetic analogues making it possible to decide which molecules will be worth synthesizing on a larger scale.
