Synthesis and characterization of monophosphinic acid DOTA derivative: A smart tool with functionalities for multimodal imaging

Publication date: 15 August 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 16
Author(s): Satya Narayana Murthy Chilla, Ondrej Zemek, Jan Kotek, Sébastien Boutry, Lionel Larbanoix, Coralie Sclavons, Luce Vander Elst, Ivan Lukes, Robert N. Muller, Sophie Laurent
A new facile synthetic strategy was developed to prepare bifunctional monophosphinic acid Ln-DOTA derivatives, Gd-DO2AGAP^NBn and Gd- DO2AGAP^ABn. The relaxivities of the Gd-complexes are enhanced compared to Gd-DOTA. Monophosphinic acid arm of these Gd-complexes affords enhancement of inner sphere water exchange rate due to its steric bulkiness. The different functionalities of DO2AGAP^NBn were appended in trans positions and are designed to conjugate identical or different vectors according to the potential applications. The conjugation of Gd-DO2AGAP^ABn with E3 peptide known to target apoptosis was successfully performed and in vivo MRI allowed cell death detection in a mouse model.

Graphical abstract

http://ift.tt/2u13WoL