serum stabilities of short tryptophan- and arginine-rich antimicrobial peptide analogs血清稳定性的色氨酸,arginine-rich抗菌多肽类似物.pdfVIP

Serum Stabilities of Short Tryptophan- and Arginine-Rich Antimicrobial Peptide Analogs 1 1 1 2 2 Leonard T. Nguyen , Johnny K. Chau , Nicole A. Perry , Leonie de Boer , Sebastian A. J. Zaat , Hans J. Vogel1* 1 Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada, 2 Department of Medical Microbiology, Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands Abstract Background: Several short antimicrobial peptides that are rich in tryptophan and arginine residues were designed with a series of simple modifications such as end capping and cyclization. The two sets of hexapeptides are based on the Trp- and Arg-rich primary sequences from the ‘‘antimicrobial centre’’ of bovine lactoferricin as well as an antimicrobial sequence obtained through the screening of a hexapeptide combinatorial library. Methodology/Principal Findings: HPLC, mass spectrometry and antimicrobial assays were carried out to explore the consequences of the modifications on the serum stability and microbicidal activity of the peptides. The results show that C- terminal amidation increases the antimicrobial activity but that it makes little difference to its proteolytic degradation in human serum. On the other hand, N-terminal acetylation decreases the peptide activities but significantly increases their protease resistance. Peptide cyclization of the hexameric peptides was found to be highly effective for both serum stability and antimicrobial activity. However the two cyclization strategies employed have different effects, with disulfide cyclization resulting in more active peptides while backbone cyclization results in more prot