title: 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.
authors.affiliation: Aparna Biosciences Corp , Rockville, MD , USA .
authors.forename: Puthupparampil V
authors.initials: PV
authors.lastname: Scaria
authors.forename: Yijia
authors.initials: Y
authors.lastname: Liu
authors.forename: Qixin
authors.initials: Q
authors.lastname: Leng
authors.forename: Szu-Ting
authors.initials: ST
authors.lastname: Chou
authors.forename: A James
authors.initials: AJ
authors.lastname: Mixson
authors.forename: Martin C
authors.initials: MC
authors.lastname: Woodle
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D016503:Drug Delivery Systems; D006639:Histidine / Q000032:analysis*; D016023:Integrins / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D016023:Integrins; D010455:Peptides; D011092:Polyethylene Glycols; D006639:Histidine
keywords: Conjugate; copolymer; fungal infections; integrin; peptide; targeting
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