Chemoselectively addressable template: a valuable tool for the engineering of molecular conjugates

The Journal of Organic Chemistry
Elisabeth GarangerP Dumy

Abstract

We herein report the modular design and the synthesis of new molecular conjugates, which can combine a cell targeting function (ligand domain) with potential cytotoxic molecules (effector domain). The present approach utilizes a cyclic peptide template, Chemoselectively Addressable Template (CAT) as a key intermediate. These CAT molecules exhibit two independent and chemically addressable domains which permits the sequential and regioselective assembly of different ligand and/or effector domains. The attachment of various units to the template was achieved by the formation of iterative oxime bonds. The chemoselective oxime bonds were produced by the reaction of glyoxylyl aldehyde groups obtained from serine precursors. The process was further developed to prevent transoximation reactions. RAFT(c[-RGDfK-])4, a synthetic vector targeting the tumor-associated a alpha(V)beta3 integrin was prepared and coupled to either a cytotoxic peptide or oligonucleotide as an illustration of present approach. The potential application of this approach has been further demonstrated by the synthesis of high molecular weight compounds such as RAFT(c[-RGDfK-])16, a alpha(V)beta3-targeting ligand of high valency index.

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Citations

Jun 23, 2006·Organic & Biomolecular Chemistry·Olivier Renaudet, Pascal Dumy
Sep 1, 2006·ChemMedChem·Jesus RazkinIsabelle Texier
Nov 22, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Didier BoturynPascal Dumy
Oct 31, 2008·Organic & Biomolecular Chemistry·Vincent DuléryTamis Darbre
Sep 30, 2008·Chembiochem : a European Journal of Chemical Biology·Pierre MuratEric Defrancq
Mar 20, 2010·Organic & Biomolecular Chemistry·Ludivine SandrinDidier Boturyn
Aug 8, 2006·Chembiochem : a European Journal of Chemical Biology·Yashveer SinghPascal Dumy
Dec 15, 2010·Chemical Communications : Chem Comm·Viviana S FluxàJean-Louis Reymond
Aug 21, 2008·Chembiochem : a European Journal of Chemical Biology·Stéphanie FoillardPascal Dumy
Dec 5, 2013·Chemistry : a European Journal·Sébastien UlrichPascal Dumy
Sep 24, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Viktorija HercegNorbert Lange
May 12, 2012·Chemical Communications : Chem Comm·Romaric BonnetEric Defrancq
Dec 1, 2012·Organic & Biomolecular Chemistry·Christiane H F WenkDidier Boturyn
Jan 5, 2008·The Journal of Organic Chemistry·Stéphanie FoillardPascal Dumy
Mar 26, 2011·Bioconjugate Chemistry·Daniela ArosioCarlo Scolastico
Apr 13, 2013·Bioconjugate Chemistry·Ouafâa El-Mahdi, Oleg Melnyk
Apr 3, 2007·Journal of the American Chemical Society·Laurent Vial, Pascal Dumy

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