N-Methylation of isoDGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent

Journal of Medicinal Chemistry
Tobias G KappHorst Kessler

Abstract

Specific targeting of the integrin subtype α5β1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective α5β1/αvβ6 peptide c(phg- isoDGR-k) into a potent peptidic RGD binding α5β1 subtype selective ligand c(phg- isoDGR-( NMe)k). Nuclear magnetic resonance spectroscopy and molecular modeling clarified the molecular basis of its improved selectivity profile. To demonstrate its potential in vivo, c(phg- isoDGR-( NMe)k) was trimerized with the chelator TRAP and used as a positron-emission tomography tracer for monitoring α5β1 integrin expression in a M21 mouse xenograft.

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Citations

Nov 4, 2020·Chembiochem : a European Journal of Chemical Biology·Saidu SaniMonique Dontenwill
Jan 8, 2021·OncoTargets and Therapy·Jianbing HouHongjuan Cui
May 8, 2021·Journal of Medicinal Chemistry·Stefano TomassiLuciana Marinelli
Jan 19, 2019·Journal of Medicinal Chemistry·Florian ReichartHorst Kessler
Jul 16, 2019·Journal of Medicinal Chemistry·Isabell KemkerNorbert Sewald
May 19, 2020·Journal of Chemical Information and Modeling·Ellen E GuestJonathan D Hirst
May 19, 2018·Journal of Medicinal Chemistry·Francesco MerlinoLuciana Marinelli
Sep 25, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Neil Gerard QuigleyJohannes Notni

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