Use of Intein-Directed Peptide Biosynthesis to Improve Serum Stability and Bioactivity of a Gelatinase Inhibitory Peptide

Author(s): Mikael Bjorklund, Heli Valtanen, Harri Savilahti, Erkki Koivunen.

Journal Name: Combinatorial Chemistry & High Throughput Screening

Volume 6 , Issue 1 , 2003

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Screening of phage display libraries allows rapid identification of peptides binding to a target. However, functional analysis of the phage sequences and their reproduction as soluble and stable peptides are often the most time-consuming part in the screening. We have used here intein-based peptide biosynthesis to produce a phage-display derived gelatinase inhibitory peptide CTTHWGFTLC and to identify the critical residues for gelatinase inhibitory activity by performing alanine-scanning mutagenesis. By biosynthetic incorporation of 5-fluorotryptophan, we obtained an inhibitor of MMP-2 and MMP-9 gelatinases that showed a 6-fold enhancement in serum stability in comparison to the wild-type peptide. The new peptide also had an improved ability to inhibit tumor cell migration. These studies indicate the utility of intein methodology for synthesis and design of peptides obtained by phage display.

Keywords: phage display, matrix metalloproteinase inhibitor, intein, peptide biosynthesis, unnatural amino acid

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Article Details

Year: 2003
Page: [29 - 35]
Pages: 7
DOI: 10.2174/1386207033329869

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