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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Development of Response-Selective Agonists of Human C5a Anaphylatoxin Conformational, Biological, and Therapeutic Considerations

Author(s): Stephen M. Taylor, Simon A. Sherman, Leonid Kirnarsky and Sam D. Sanderson

Volume 8 , Issue 6 , 2001

Page: [675 - 684] Pages: 10

DOI: 10.2174/0929867013373156

Price: $65

Abstract

Numerous studies on the relationship between the structure and function of peptide agonists derived from the biologically active, C-terminal region of human C5a anaphylatoxin have been reported over the past decade. These studies have been performed with the objective of parlaying this structure-function information into the design of peptide-peptidomimetic modulators of C5a receptor (C5aR)-mediated function. In this review, we describe a rational approach for the development of conformationally biased, decapeptide agonists of C5a and described how these stabilized and specific conformational features relate to the expression of specific C5a-like activities in vitro and in vivo. The therapeutic potential of such response-selective C5a agonists is discussed and underscored by the results of one such response-selective C5a agonist that was used in vivo as an effective molecular adjuvant capable of generating antigen-specific humoral and cellular immune responses. Finally, we describe the synthesis of a new generation of highly response-selective, conformationally biased C5a agonist and discuss the in vitro and in vivo biologic results that so indicate this biologic selectivity.

Keywords: Human C5a, Anaphylatoxin, Immunoinflammatory response, Peptide Agonist design, Antibody Humoral Response


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