1. Generating Chemokine Analogs with Enhanced Pharmacological Properties Using Phage Display
- Author
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Fabrice Cerini, Guy Gorochov, Karim Dorgham, Irène Rossitto-Borlat, Hubert François Gaertner, Oliver Hartley, Astrid Melotti, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Structural Biology and Bioinformatics, Structural Biology and Bioinformatics, Department of Pathology and Immunology, and University of Geneva [Switzerland]
- Subjects
0301 basic medicine ,Library design ,Chemokine ,Phage display ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,biology ,[SDV]Life Sciences [q-bio] ,Receptor signaling ,Computational biology ,Bioinformatics ,03 medical and health sciences ,030104 developmental biology ,CX3CR1 ,biology.protein ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,Peptide library ,ComputingMilieux_MISCELLANEOUS - Abstract
Phage display technology, which allows extremely rare ligands to be selected from libraries of variants according to user-defined selection criteria, has made a huge impact on the life sciences. In this chapter, we describe phage display methods for the discovery of chemokine analogs with enhanced pharmacological properties. We discuss strategies for chemokine library design and provide a recommended technique for library construction. We also describe cell-based library selection approaches that we have used to discover chemokine analogs, not only receptor antagonists but also variants with unusual effects on receptor signaling and trafficking. By providing a survey of the different phage chemokine projects that we have undertaken, we comment on the parameters most likely to affect success. Finally, we discuss how phage display-derived chemokine analogs with altered pharmacological activity represent valuable tools to better understand chemokine biology, and why certain among them have the potential to be developed as new medicines.
- Published
- 2016
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