Molecular design opportunities presented by solvent-exposed regions of target proteins

Xiangyi Jiang; Ji Yu; Zhongxia Zhou; Jacob Kongsted; Yuning Song; Christophe Pannecouque; Erik De Clercq; Dongwei Kang; Vasanthanathan Poongavanam; Xinyong Liu; Peng Zhan

doi:10.1002/med.21581

Molecular design opportunities presented by solvent-exposed regions of target proteins

Med Res Rev. 2019 Nov;39(6):2194-2238. doi: 10.1002/med.21581. Epub 2019 Apr 19.

Authors

Affiliations

¹ Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People's Republic of China.
² Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark.
³ Department of Clinical Pharmacy, Qilu Hospital of Shandong University, Jinan, China.
⁴ Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.

PMID: 31002405
DOI: 10.1002/med.21581

Abstract

Solvent-exposed regions, or solvent-filled pockets, within or adjacent to the ligand-binding sites of drug-target proteins provide opportunities for substantial modifications of existing small-molecular drug molecules without serious loss of activity. In this review, we present recent selected examples of exploitation of solvent-exposed regions of proteins in drug design and development from the recent medicinal-chemistry literature.

Keywords: drug design; medicinal chemistry; protein/solvent interface; solvent-accessible region; solvent-exposed region; solvent-filled pocket.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Drug Delivery Systems
Drug Design*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Models, Molecular
Proteins / chemistry*
Solvents / chemistry*

Substances

Enzyme Inhibitors
Proteins
Solvents