Too sweet: cheminformatics for deglycosylation in natural products
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Journal of Cheminformatics Open Access
RESEARCH ARTICLE
Too sweet: cheminformatics for deglycosylation in natural products Jonas Schaub1 , Achim Zielesny2 , Christoph Steinbeck1* and Maria Sorokina1*
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. Keywords: Natural products, Sugars, Carbohydrates, Deglycosylation, Cheminformatics, Chemistry Development Kit, CDK Introduction Sugar is a general term that refers to a carbohydrate with the generic molecular formula C n(H2O)n. They are generally produced by living organisms and are mainly associated with sweet taste, but their function spreads way further than sweetening our palates. Indeed, only a few sugars, when in a solid or liquid state, taste “sweet”, among them glucose, fructose, or lactose. However, most of the sugar molecules are non-odorous and unsweet. Sugars are also very often found as substituents of small molecules produced by living organisms—for example, deoxyribose, the DNA building block. Furthermore, it is widely accepted [1–6] that sugar moieties are one of the most typical structural characteristics of biological molecules, and in particular of natural products (NPs). The latter are small molecules that have “higher” functions, such as signalling, intercellular and inter-organism *Correspondence: christoph.steinbeck@uni‑jena.de; maria.sorokina@uni‑jena. de 1 Institute for Inorganic and Analytical Chemistry, Friedrich-Schiller University, Lessing Strasse 8, 07743 Jena, Germany Full list of author information is available at the end of the article
communication, or defence. For instance, they inspire the pharmaceutical industry and research [7], and therefore their structural characteristics and the substituents from which they derive their activities are being intensely studied. There is evidence that the presence of stereo-diverse sugar units in aglycons (molecular structures without sugar substituents) affects their pharmacokinetic properties by making them more soluble [3] and being involved in transport, target specificity, in ligand-target interactions, and in particular, in the receptor binding [2, 8, 9]. However, in most of the cases, sugar units do not affect the principal activity of the aglycon [10] and importantly, may obstruct compo
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