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Nitric Oxide-Releasing Hyperbranched Polyaminoglycosides for Antibacterial Therapy

Nitric Oxide-Releasing Hyperbranched Polyaminoglycosides for Antibacterial Therapy

Lei Yang, Mark H Schoenfisch

ACS Appl Bio Mater. 2018 Oct 15;1(4):1066-1073.

PMID: 32309793

Abstract:

Hyperbranched polyaminoglycosides were prepared by the polymerization of kanamycin, gentamicin, and neomycin, and N,N'-methylenebis(acrylamide) via a one-pot reaction. The secondary amines at the linear units of the hyperbranched polymers were subsequently reacted with NO gas at high pressure under alkaline conditions to form N-diazeniumdiolate NO donors. The resulting NO-releasing hyperbranched polyaminoglycosides exhibited a wide range of NO payloads (~0.4-1.3 µmol mg-1) and release kinetics (half-lives ~70-180 min). The therapeutic utility of these materials was evaluated by examining their bactericidal activity against common dental pathogens and toxicity to human gingival fibroblast cells. The antibacterial efficacy of NO-releasing hyperbranched polyaminoglycosides was dependent on specific physiochemical properties, with greater degrees of branching and aminoglycoside terminal groups correlating to enhanced action. Nitric oxide-releasing hyperbranched polykanamycin and polyneomycin elicited the least cytotoxicity at bactericidal concentrations, indicating the greatest therapeutic index for future biomedical applications.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS76282	Hyperbranched G6-PEG6k-OH			Price

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