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Enhancement of antifungal activity by integrin-targeting of branched histidine rich peptides.

ABSTRACT: The treatment of invasive candidiasis associated with growing numbers of immunocompromised patients remains a major challenge complicated by increasing drug resistance. A novel class of branched histidine-lysine (bHK) peptides has promising antifungal activity, and exhibits a mechanism similar to natural histatins, and thus may avoid drug resistance. The present studies evaluate ligand targeting of bHK peptides to fungal surface integrins by determining whether a cyclic RGD (cRGD) peptide with a large PEG linker could enhance bHK peptide antifungal activity. Whereas conjugates containing only the PEG linker reduced bHK peptide activity, conjugates with the cRGD-PEG ligand resulted in marked enhancement of activity against Candida albicans. This study provides the first demonstration of benefit from ligand targeting of antifungal agents to fungal surface receptors.

SUBMITTER: Scaria PV

PROVIDER: S-EPMC4072455 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Enhancement of antifungal activity by integrin-targeting of branched histidine rich peptides.

Scaria Puthupparampil V PV Liu Yijia Y Leng Qixin Q Chou Szu-Ting ST Mixson A James AJ Woodle Martin C MC

Journal of drug targeting 20140414 6

The treatment of invasive candidiasis associated with growing numbers of immunocompromised patients remains a major challenge complicated by increasing drug resistance. A novel class of branched histidine-lysine (bHK) peptides has promising antifungal activity, and exhibits a mechanism similar to natural histatins, and thus may avoid drug resistance. The present studies evaluate ligand targeting of bHK peptides to fungal surface integrins by determining whether a cyclic RGD (cRGD) peptide with a ...[more]

PMID: 24731059

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