Work

Stereochemical diversity as a source of discovery in chemical biology

Year: 2022

Type: article

Abstract: Chirality is an inherent aspect of biology, and interactions between biomolecules are often influenced by stereochemistry and topographic complexity. This has implications for how small-molecule libraries are assembled for screening campaigns in chemical biology and drug discovery. Here we review the state of the field in the context of harnessing chirality as a source of chemical information at the chemistry-biology interface. We further highlight the emergence of screening libraries containing stereoisomeric sets of compounds and the concept of using stereoselectivity of phenotype and/or target engagement as a way to prioritize actionable targets and streamline the identification of selective and potent modulators of disease-relevant biomolecules. The chemical information density of FDA-approved drugs and the effect of stereochemistry on molecular complexity are reported. Finally, axial chirality and atroposelectivity are discussed as potential expansions of the aforementioned concepts.

Source: Current Research in Chemical Biology

DOI: 10.1016/j.crchbi.2022.100028

Authors: Kevin A. Scott, Nathalie Ropek, Bruno Melillo, Stuart L. Schreiber, Benjamin F. Cravatt, Ekaterina V. Vinogradova

Institutions: Rockefeller University, Broad Institute, Scripps Research Institute, Harvard University

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $1,850

Funders: Irma T. Hirschl Trust, Robertson Foundation, Searle Scholars Program, National Institutes of Health