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Discovery of Synthetic Penaeidin Activity against Antibiotic‐resistant Fungi
Author(s) -
Cuthbertson Brandon J.,
Büllesbach Erika E.,
Gross Paul S.
Publication year - 2006
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2006.00417.x
Subject(s) - biology , antimicrobial peptides , peptide , context (archaeology) , antimicrobial , microbiology and biotechnology , biochemistry , paleontology
Penaeidins are antimicrobial peptides from shrimp that are constituted by divergent classes of peptide isoforms in an individual organism. Penaeidin sequence variation suggests functional diversity in the host and promises differential activities if applied to treat infections in humans. We have synthesized isoform 4 of penaeidin class 3 from the Atlantic shrimp, Litopenaeus setiferus , by native ligation using three peptide segments. Our synthesis approach led to the discovery of an irreversible side reaction that was successfully suppressed, a discovery, which has particular relevance to the synthesis of cysteine‐rich peptides. The antimicrobial activity of full‐length penaeidin and the N‐terminal proline‐rich domain of this isoform were compared with the corresponding peptides of penaeidin class 4 isoform 1 using a wide range of bacteria and fungi. New aspects of penaeidin function are reported that include activity against fungi of the phylum Basidiomycota ( Cryptococcus strains), activity against fungi that are pathogenic to humans and effectiveness in the context of antibiotic resistance mechanisms ( Cryptococcus and Candida spp.). The proline‐rich domain of penaeidin class 4 shows the highest relative antimicrobial activity, while exhibiting no cytotoxicity to human monocytes, and therefore stands out as a potential peptide therapeutic.