title: Divergent oriented synthesis for the design of reagents for protein conjugation.
abstract: Instead of using diversity oriented syntheses (DOS) to obtain compounds with biological activities, we employed the DOS method to efficiently obtain multifunctional single attachment point (MSAP) reagents for the conjugation to proteins. Acid insensitive functional groups (chelators, fluorochromes) were attached to Lys-Cys-NH(2) or Lys-Lys-betaAla-Cys-NH(2) peptide scaffolds. After cleavage from solid supports, the modified peptide intermediates were split and further modified by two solution phase, chemoselective reactions employing the single amine and single thiol presented on the intermediates. MSAP-based fluorochrome-chelates were obtained, some possessing a third functional group like a polyethylene glycol (PEG) polymer or "click chemistry" reactive alkynes and azides. The DOS of MSAP reagents permitted the efficient generation of panels of MSAP reagents that can be used to obtain multifunctional proteins with a single modified amino acid (a single attachment point).
authors.affiliation: Laboratoire de Chimie des Polymeres Organiques (LCPO), UMR 5629 CNRS, IPB/ENSCBP, Universite Bordeaux I, Pessac Cedex, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Garanger
authors.forename: Joseph
authors.initials: J
authors.lastname: Blois
authors.forename: Scott A
authors.initials: SA
authors.lastname: Hilderbrand
authors.forename: Fangwei
authors.initials: F
authors.lastname: Shao
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
mesh_terms: D002614:Chelating Agents / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry*; D015195:Drug Design; D005456:Fluorescent Dyes / Q000737:chemistry; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*
chemical_list: D002614:Chelating Agents; D003432:Cross-Linking Reagents; D005456:Fluorescent Dyes; D010455:Peptides; D011506:Proteins