Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 43, 2013
Previous Article Next Article

Chemical–physical analysis of a tartrate model compound for TACE inhibition

Author affiliations

Abstract

We have synthesized and done an extensive chemical–physical analysis of the behavior of a new compound, named MBET306, a synthetic precursor of the recently discovered tartrate-based inhibitors of the protein Tumor Necrosis factor-α Converting Enzyme (TACE). Experimental and theoretical data have shown that in water solution MBET306 is overwhelmingly found as a monoanion at physiological pH, in a conformation that differs substantially from that detected in the known co-crystal structures of MBET306 derivatives bound to TACE. The body of collected experimental and theoretical data indicates that the monoanionic species binds Zn(II) inducing a strong stabilization of the crystal-like arrangement of the central tartrate zinc-binding group, lending support for a two step TACE docking mechanism via a zinc-bound intermediate. The thorough chemical–physical characterization of the conformational behavior of free and zinc-bound MBET306 in water bulk solution opens new avenues for the rational drug design of tartrate-based highly specific TACE inhibitors.

Graphical abstract: Chemical–physical analysis of a tartrate model compound for TACE inhibition

Back to tab navigation

Supplementary files

Article information


Submitted
15 Jul 2013
Accepted
05 Sep 2013
First published
11 Sep 2013

Phys. Chem. Chem. Phys., 2013,15, 18881-18893
Article type
Paper

Chemical–physical analysis of a tartrate model compound for TACE inhibition

M. Banchelli, C. Guardiani, E. Tenori, S. Menichetti, G. Caminati and P. Procacci, Phys. Chem. Chem. Phys., 2013, 15, 18881
DOI: 10.1039/C3CP52955J

Social activity

Search articles by author

Spotlight

Advertisements