Metallodrugs having improved pharmacological properties and methods of manufacture and use thereof

摘要

It is an object of the present invention to provide antimicrobial metallodrugs comprising an antimicrobial peptide (“AMP”) and/or an antibiotic covalently bound to a metal binding moiety. These metallodrugs combine a metal binding domain which typically catalyzes oxido-reductase chemistry or acts as a Lewis-Acid catalyst, with a member of a diverse class of antimicrobial agents currently validated in preclinical and clinical settings for the treatment of a broad spectrum of pathogenic organisms.

主权项

1. An antimicrobial composition, comprising:
a first moiety which is (i) an antimicrobial peptide (“AMP”), or peptide that binds to a pathogenic target, the sequence of which is between 6 and 100 amino acids, is net positively charged, and is amphipathic, (ii) an antibiotic, or (iii) a conjugate comprising an AMP, or peptide that binds to a pathogenic target, and an antibiotic; and a second moiety which is a metal binding moiety selected from the group consisting of a peptide motif, a cyclam, a cyclen, and a non-porphyrin macrocyclic chelating agent, wherein the first moiety and the second moiety are covalently linked to form a complex, wherein the second moiety is heterologous to the first moiety, wherein the first moiety and the second moiety act separately, with distinct functions, in such a way that the second moiety enhances the antimicrobial effects of the first moiety, and wherein the first moiety promotes uptake of the complex into a target cell or organelle.