Issue 31, 2020
From the journal:

Chemical Communications

Water envelope has a critical impact on the design of protein–protein interaction inhibitors†

Ekaterina L. Ratkova, ORCID logo *ab   Maciej Dawidowski, ORCID logo ac   Valeria Napolitano,d   Grzegorz Dubin, ORCID logo d   Roberto Fino,a   Michael S. Ostertag,a   Michael Sattler,ae   Grzegorz Popowicz*a  and  Igor V. Tetko ORCID logo *af  

* Corresponding authors

a Institute of Structural Biology, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, 85764 Neuherberg, Germany
E-mail: grzegorz.popowicz@helmholtz-muenchen.de, i.tetko@helmholtz-muenchen.de

b Medicinal Chemistry, Cardiovascular, Renal and Metabolic Diseases, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden
E-mail: ekaterina.ratkova@astrazeneca.com

c Department of Drug Technology and Pharmaceutical Biotechnology, Medical University of Warsaw, Banacha 1, 02-097 Warszawa, Poland

d Faculty of Biochemistry, Biophysics and Biotechnology and Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland

e Center for Integrated Protein Science Munich at Chair of Biomolecular NMR, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany

f BIGCHEM GmbH, Valerystr. 49, 85716 Unterschleißheim, Germany

Abstract

We show that a water envelope network plays a critical role in protein–protein interactions (PPI). The potency of a PPI inhibitor is modulated by orders of magnitude on manipulation of the solvent envelope alone. The structure–activity relationship of PEX14 inhibitors was analyzed as an example using in silico and X-ray data.

Graphical abstract: Water envelope has a critical impact on the design of protein–protein interaction inhibitors

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Article information

DOI
https://doi.org/10.1039/C9CC07714F
Article type
Communication
Submitted
02 Oct 2019
Accepted
10 Mar 2020
First published
20 Mar 2020
This article is Open Access
Creative Commons BY-NC license

Chem. Commun., 2020,56, 4360-4363

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Water envelope has a critical impact on the design of protein–protein interaction inhibitors

E. L. Ratkova, M. Dawidowski, V. Napolitano, G. Dubin, R. Fino, M. S. Ostertag, M. Sattler, G. Popowicz and I. V. Tetko, Chem. Commun., 2020, 56, 4360 DOI: 10.1039/C9CC07714F

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