tailieunhanh - Báo cáo khoa học: Selection of a CXCR4 antagonist from a human heavy chain CDR3-derived phage library

Phage display technology is a powerful selection approach to identify strong and specific binders to a large variety of targets. In this study, we compared the efficacy of a phage library displaying human heavy chain complementarity determining region 3 (HCDR3) repertoires with a set of conventional random peptide libraries for the identification of CXCR4 | IFEBS Journal Selection of a CXCR4 antagonist from a human heavy chain CDR3-derived phage library Andy Chevigne1 Aurelie Fischer1 Julie Mathu1 Manuel Counson1 Nadia Beaupain1 Jean-Marc Plesseria1 Jean-Claude Schmit1 2 and Sabrina Deroo1 1 Laboratoire de Retrovirologie Centre de Recherche Public-Sante Luxembourg Luxembourg 2 Service Nationaldes Maladies Infectieuses Centre Hospitalier Luxembourg Luxembourg Keywords CXCR4 antagonist HCDR3 natural sequence randomization peptide repertoire phage display Correspondence A. Chevigne Laboratoire de Retrovirologie Centre de Recherche Public-Sante 84 Val Fleuri L-1526 Luxembourg Luxembourg Fax 352 26970 221 Tel 352 26970 336 E-mail Received 16 March 2011 revised 27 May 2011 accepted 6 June 2011 doi Phage display technology is a powerful selection approach to identify strong and specific binders to a large variety of targets. In this study we compared the efficacy of a phage library displaying human heavy chain complementarity determining region 3 HCDR3 repertoires with a set of conventional random peptide libraries for the identification of CXCR4 antagonists using a peptide corresponding to the second extracellular loop of the receptor CXCR4 as target. A total of 11 selection campaigns on this target did not result in any specific ligand from the random peptide libraries. In contrast a single selection campaign with an HCDR3 library derived from the IgM repertoire of a nonimmunized donor resulted in nine specific peptides with lengths ranging from 10 to 19 residues. Four of these HCDR3 sequences interacted with native receptor and the most frequently isolated peptide displayed an affinity of IM and acted as a CXCR4 antagonist IC50 23 im . To comprehend the basis of the highly efficient HCDR3 library selection its biochemical properties were investigated. The HCDR3 length varied from 3 to 21 residues and displayed a biased amino acid content with a predominant .