학술논문

Enhancement of antifungal activity by integrin-targeting of branched histidine rich peptides.
Document Type
Article
Source
Journal of Drug Targeting. Jul2014, Vol. 22 Issue 6, p536-542. 7p.
Subject
*PEPTIDES
*INTEGRINS
*ANTIFUNGAL agents
*INVASIVE candidiasis
*CANDIDIASIS treatment
*IMMUNOCOMPROMISED patients
*COPOLYMERS
*HISTIDINE
*THERAPEUTICS
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]