학술논문
Enhancement of antifungal activity by integrin-targeting of branched histidine rich peptides.
Document Type
Article
Author
Source
Subject
*PEPTIDES
*INTEGRINS
*ANTIFUNGAL agents
*INVASIVE candidiasis
*CANDIDIASIS treatment
*IMMUNOCOMPROMISED patients
*COPOLYMERS
*HISTIDINE
*THERAPEUTICS
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Language
ISSN
1061-186X
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. [ABSTRACT FROM AUTHOR]