A peptide inhibitor of cholesteryl ester transfer protein identified by screening a bacteriophage display library

• Published in: The journal of peptide research Vol. 51; no. 3; pp. 216 - 225
• Main Authors: BONIN, PAUL D., BANNOW, CAROL A., SMITH, CLARK W., FISCHER, H. DAVID, ERICKSON, LAURENCE A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-1998
• Subjects: Amino Acid Sequence; Animals; bacteriophage display library; Carrier Proteins - antagonists & inhibitors; Carrier Proteins - metabolism; CHO Cells; Cholesterol Ester Transfer Proteins; Cholesterol Esters - metabolism; cholesteryl ester transfer protein; Coliphages - genetics; Cricetinae; Escherichia coli - virology; Glycoproteins; Macaca fascicularis; Oligopeptides - metabolism; peptide inhibitor; Peptide Library; Protein Binding; Triglycerides - metabolism
• ISSN: 1397-002X; 1399-3011
• DOI: 10.1111/j.1399-3011.1998.tb01219.x

We screened a bacteriophage display library of random decapeptides to identify peptide inhibitors of cholesteryl ester transfer protein (CETP). After affinity selection against CETP, bacteriophage‐infected Escherichia coli were plated at clonal density and 36 random clones were isolated. Analysis of the relevant portion of the bacteriophage DNA from a group of 12 clones that had a relatively high affinity for CETP revealed that the corresponding amino acid sequences of the displayed peptides exhibited an. Xaa‐Arg‐Met‐Arg‐Tyr‐Xaa composite motif. Based on those results, decapeptides from this group were synthesized and one of them, DPI (NH2‐VTWRMWYVPA‐COOH), inhibited CETP‐catalyzed transfer of cholesteryl esters and triglycerides. Amino‐ and carboxy‐terminal truncations of DPI demonstrated that the original decapeptide could be reduced to a pentapeptide without loss of either its ability to bind to CETP or its ability to inhibit CETP‐mediated lipid transfer. That pentapeptide, NH2‐WRMWY‐COOH (WRMWY, PNU‐107368E), binds directly to CETP and its inhibition is consistent with that of a competitive inhibitor of CETP with a Ki of 164 μm. WRMWY or modified versions of this peptide may be useful in studying the interactions between CETP and plasma lipoproteins.