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Journal of Biochemistry Advance Access originally published online on October 9, 2008
Journal of Biochemistry 2008 144(6):781-788; doi:10.1093/jb/mvn134
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© The Authors 2008. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

Modification of Antimicrobial Peptide with Low Molar Mass Poly(ethylene glycol)

Genghui Zhang1,2, Baozhong Han1,2, Xiaoyan Lin1,2, Xin Wu1,2 and Husheng Yan1,2,*

1Key Laboratory of Functional Polymer Materials, Ministry of Education; and 2Institute of Polymer Chemistry, Nankai University, Tianjin 300071, P. R. China

*To whom correspondence should be addressed. Tel: +86-22-23501705, Fax: +86-22-23503510, E-mail: yanhs{at}nankai.edu.cn

Received July 16, 2008; Accepted September 23, 2008


  Abstract

PEGylation of peptide drugs prolongs their circulating lifetimes in plasma. However, PEGylation can produce a decrease in the in vitro bioactivity. Longer poly(ethylene glycol) (PEG) chains are favourable for circulating lifetimes but unfavourable for in vitro bioactivities. In order to circumvent the conflicting effects of PEG length, a hydrophobic peptide, using an antimicrobial peptide as a model, was PEGylated with short PEG chains. The PEGylated peptides self-assembled in aqueous solution into micelles with PEG shell and peptide core. In these micelles, the core peptides were protected by the shell, thus reducing proteolytic degradation. Meanwhile, most of the in vitro antimicrobial activities still remained due to the short PEG chain attached. The stabilities of the PEGylated peptides were much higher than that of the unPEGylated peptides in the presence of chymotrypsin and serum. The antimicrobial activities of the PEGylated peptides in the presence of serum, an ex vivo assay, were much higher than that of the unPEGylated peptide.

Key Words: antimicrobial peptides, micelles, PEGylation, peptides, self-assembly

Abbreviations: CD, circular dichroism; CFU, colony form unit; CMC, critical micelle concentration; DBU, 1,8-diazabicyclo [5,4,0] undec-7-ene; DCM, dichloromethane; DIC, diisopropyl carbodiimide; DLS, dynamic laser scattering; DMF, dimethylformamide; DMSO, dimethyl sulfoxide; FDA, Food and Drug Administration; Fmoc, 9-Fluorenylmethyloxycarbonyl; HEPES, 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid; MIC, minimal inhibitory concentration; mPEG-COOH, monomethoxy poly(ethylene glycol) carboxylic acid; PBS, phosphate-buffered saline; PEG, poly(ethylene glycol); TEM, transmission electron microscopy; TFA, trifluoroacetic acid


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