Too sweet: cheminformatics for deglycosylation in natural products

Abstract

Sugar units in natural products are pharmacokinetically important but often redundant and therefore obstructing the study of the structure and function of the aglycon. Therefore, it is recommended to remove the sugars before a theoretical or experimental study of a molecule. Deglycogenases, enzymes that specialized in sugar removal from small molecules, are often used in laboratories to perform this task. However, there is no standardized computational procedure to perform this task in silico. In this work, we present a systematic approach for in silico removal of ring and linear sugars from molecular structures. Particular attention is given to molecules of biological origin and to their structural specificities. This approach is made available in two forms, through a free and open web application and as standalone open-source software.

Description and Analysis of Glycosidic Residues in the Largest Open Natural Products Database

“…For the detection and removal of glycosidic moieties in the molecular datasets, the open-source software Sugar Removal Utility [ 18 ] (SRU) was used. Based on the Chemistry Development Kit [ 19 ] (CDK), it consists of a generalised and configurable approach for in silico detection and removal of circular and linear sugar moieties from chemical structures.…”

Pseudo-Natural Products Occur Frequently in Biologically Relevant Compounds

“…Then, metal atoms were disconnected from the structures and organic non-linear minor compounds were extracted from mixtures, when applicable. To remove sugar units in NPs 31 , an in-house script was developed using the RDKit, to detect sugar-like rings and peel them off iteratively, starting from the outer layer on the molecule. A set of filters was then applied to remove unwanted entries, based on the number of heavy atoms (x ≥ 4, 0.03%), molecular weight (x ≤ 1000.0 Da, 1.25%), number of rings (x ≥ 1, 7.26%) and chemical elements (only authorized: H, B, C, N, O, F, P, S, Cl, Br, I, 0.08%).…”