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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Chemical synthesis, structure-activity relationship, and properties of shepherin I: a fungicidal peptide enriched in glycine-glycine-histidine motifs

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Author(s):
Remuzgo, Cesar [1] ; Oewel, Thais S. [1] ; Daffre, Sirlei [2] ; Lopes, Thiago R. S. [1] ; Dyszy, Fabio H. [3] ; Schreier, Shirley [3] ; Machado-Santelli, Glaucia M. [4] ; Teresa Machini, M. [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Lab Peptide Chem, BR-05513970 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05513970 Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Chem, Dept Biochem, Struct Biol Lab, BR-05513970 Sao Paulo - Brazil
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05513970 Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Amino Acids; v. 46, n. 11, p. 2573-2586, NOV 2014.
Web of Science Citations: 16
Abstract

Although glycine-rich antimicrobial peptides (AMPs) are found in animals and plants, very little has been reported on their chemistry, structure activity-relationship, and properties. We investigated those topics for Shepherin I (Shep I), a glycine-rich AMP with the unique amino acid sequence G(1)YGGHGGHGGHGGHGGHGGH-GHGGGGHG(28). Shep I and analogues were synthesized by the solid-phase method at 60 degrees C using conventional heating. Purification followed by chemical characterization confirmed the products' identities and high purity. Amino acid analysis provided their peptide contents. All peptides were active against the clinically important Candida species, but ineffective against bacteria and mycelia fungi. Truncation of the N- or C-terminal portion reduced Shep I antifungal activity, the latter being more pronounced. Carboxyamidation of Shep I did not affect the activity against C. albicans or C. tropicalis, but increased activity against S. cerevisiae. Carboxyamidated analogues Shep I (3-28) a and Shep I (6-28) a were equipotent to Shep I and Shep Ia against Candida species. As with most cationic AMPs, all peptides had their activity significantly reduced in high-salt concentrations, a disadvantage that is defeated if 10 mu M ZnCl2 is present. At 100 mu M, the peptides were practically not hemolytic. Shep Ia also killed C. albicans MDM8 and ATCC 90028 cells. Fluo-Shep Ia, an analogue labeled with 5(6)-carboxyfluorescein, was rapidly internalized by C. albicans MDM8 cells, a salt-sensitive process dependent on metabolic energy and temperature. Altogether, such results shed light on the chemistry, structural requirements for activity, and other properties of candidacidal glycinerich peptides. Furthermore, they show that Shep Ia may have strong potential for use in topical application. (AU)

FAPESP's process: 08/11695-1 - Alternative technologies in peptide chemistry: metal ion-promoted solvolysis, biocatalysis, conventional heating and microwave heating
Grantee:Maria Teresa Machini
Support Opportunities: Regular Research Grants