A peptide inhibitor of cholesteryl ester transfer protein identified by screening a bacteriophage display library
| Autor: | H. David Fischer, Laurence A. Erickson, Paul D. Bonin, Carol A. Bannow, Clark W. Smith |
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| Rok vydání: | 1998 |
| Předmět: |
Peptide
CHO Cells Biology medicine.disease_cause Biochemistry Pentapeptide repeat Coliphages Bacteriophage chemistry.chemical_compound Endocrinology Peptide Library Cricetinae Cholesterylester transfer protein medicine Escherichia coli Animals Amino Acid Sequence Triglycerides Glycoproteins chemistry.chemical_classification Peptide inhibitor biology.organism_classification Molecular biology Amino acid Cholesterol Ester Transfer Proteins carbohydrates (lipids) Macaca fascicularis chemistry biology.protein lipids (amino acids peptides and proteins) Cholesterol Esters Carrier Proteins Oligopeptides DNA Protein Binding |
| Zdroj: | The journal of peptide research : official journal of the American Peptide Society. 51(3) |
| ISSN: | 1397-002X |
| Popis: | 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, DP1 (NH2-VTWRMWYVPA-COOH), inhibited CETP-catalyzed transfer of cholesteryl esters and triglycerides. Amino- and carboxy-terminal truncations of DP1 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 microM. WRMWY or modified versions of this peptide may be useful in studying the interactions between CETP and plasma lipoproteins. |
| Databáze: | OpenAIRE |
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