Nitric oxide-releasing polyaminoglycosides as biodegradable antibacterial scaffolds and methods pertaining thereto
AssigneeThe University of North Carolina at Chapel Hill
InventorsMark H. Schoenfisch, Lei Yang
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Abstract
Provided herein are hyperbranched polyaminoglycosides, where in some embodiments, the hyperbranched polyaminoglycosides are covalently modified to store and release nitric oxide. Some embodiments pertain to methods of making and use of hyperbranched polyaminoglycosides. In some embodiments, the covalently modified hyperbranched polyaminoglycosides may be tailored to release nitric oxide in a controlled manner and are useful for eradication of both gram positive and gram negative bacteria as well as other microbes.
Claims15
A hyperbranched polyaminoglycoside, comprising a first aminoglycoside unit comprising Formula II:
- wherein each of R1, R2, R3, R4, R5, R6, R9, and R10 is independently selected from —H or represents a covalent bond to one or more linking units;
- wherein a linking unit of the one or more linking units is represented by the following structure:
- wherein at least one linking unit forms a covalent bridge between the first aminoglycoside unit and a second aminoglycoside unit;
- and
- wherein at least one aminoglycoside unit of the hyperbranched polyaminoglycoside is derived from kanamycin;
- wherein at least one aminoglycoside unit of the hyperbranched polyaminoglycoside comprises one or more terminal units selected from:
- and
- wherein at least a secondary amine of the hyperbranched polyaminoglycoside comprises a N-diazeniumdiolate NO donor.
A hyperbranched polyaminoglycoside, comprising a first aminoglycoside comprising a structure of Formula I:
- wherein G1 is selected from the group consisting of:
- wherein G2 is selected from the group consisting of:
- R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of —H, optionally substituted C1-C6 alkyl, optionally substituted polyamino having 1 to 6 repeat units with intervening C1-C6 alkyl groups, optionally substituted polyether having 1 to 6 repeat units with intervening C1-C6 alkyl groups, and a covalent bond to a linking unit;
- Xa, Xb, and Xc are independently selected from —H, —OH, and C1-C6 alkyl;
- wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 is a covalent bond to one or more linking unit selected from the group consisting of:
- wherein “” indicates an attachment to the first aminoglycoside;
- W1, W2, or W3, where present, are independently selected from one or more additional aminoglycosides or one or more end-capping substituents and at least one linking unit provides a covalent bridge from the first aminoglycoside to a second aminoglycoside;
- Ra, Rb, and Rc are independently selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted polyamino having 1 to 6 repeat units (with C1-C6 alkyl(s)), or optionally substituted polyether having 1 to 6 repeat units (with C1-C6) alkyl(s));
- and
- wherein the one or more end-capping substituents, where present, independently have a formula of —NH—((CH2)aX1)b—(CH2)cH where X1 is O or NH and a, b, and c are independently an integer from 0 to 10, and
- wherein said hyperbranched polyaminoglycoside further comprises a NO-donating group, and
- wherein at least one aminoglycoside unit of the hyperbranched polyaminoglycoside comprises one or more terminal units selected from:
Dependencies are inferred from the claim text.