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Multivalency—a way to enhance binding avidities and bioactivity—preliminary applications to EPO
Author(s) -
Vadas Oscar,
Rose Keith
Publication year - 2007
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.794
Subject(s) - chemistry , erythropoietin receptor , peptide , avidity , monomer , receptor , erythropoietin , combinatorial chemistry , sequence (biology) , biological activity , stereochemistry , computational biology , biochemistry , in vitro , biology , polymer , organic chemistry , antibody , immunology , endocrinology
Multivalency has advantages over monovalency for binding interactions and even for activity. In particular, avidity is higher since the off‐rate of a multivalent species is much slower than that of a monomer. This is particularly profitable for ligand‐binding receptors that require dimerization for activity, such as the receptor of erythropoietin (EPOR). Peptides that mimic the action of erythropoietin (EPO) have been described with no sequence similarity with the human hormone: erythropoietin mimetic peptide (EMP) and EPO receptor peptide (ERP). These two peptides have similar activity but interact through different sites on the EPOR. Here, we describe the construction of several new synthetic homo‐ and hetero‐dimers based on EMP‐ERP sequences. To link the monomeric molecules together, several monodisperse polyamide linkers of different lengths were synthesized with dialdehyde functionalities. Chemoselective oxime chemistry was used to obtain homogeneous constructs. Certain chemical incompatibilities were dealt with via a protection approach. The oximes are stable under normal conditions and so lend themselves to biological testing. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.