Glycans in drug discovery

Valverde, Pablo; Ardá, Ana; Reichardt, Niels‐Christian; Jiménez‐Barbero, Jesús; Gimeno, Ana

doi:10.1039/c9md00292h

Cited by 73 publications

(74 citation statements)

References 170 publications

(134 reference statements)

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“…Most drugs are small organic molecules. However, drugs can also be macromolecular in nature, such as glycans (also referred to as carbohydrates) [95] or synthetic polymers [96].…”

Section: Key Macromoleculesmentioning

confidence: 99%

Molecular representations in AI-driven drug discovery: a review and practical guide

et al. 2020

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The technological advances of the past century, marked by the computer revolution and the advent of high-throughput screening technologies in drug discovery, opened the path to the computational analysis and visualization of bioactive molecules. For this purpose, it became necessary to represent molecules in a syntax that would be readable by computers and understandable by scientists of various fields. A large number of chemical representations have been developed over the years, their numerosity being due to the fast development of computers and the complexity of producing a representation that encompasses all structural and chemical characteristics. We present here some of the most popular electronic molecular and macromolecular representations used in drug discovery, many of which are based on graph representations. Furthermore, we describe applications of these representations in AI-driven drug discovery. Our aim is to provide a brief guide on structural representations that are essential to the practice of AI in drug discovery. This review serves as a guide for researchers who have little experience with the handling of chemical representations and plan to work on applications at the interface of these fields.

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“…Most drugs are small organic molecules. However, drugs can also be macromolecular in nature, such as glycans (also referred to as carbohydrates) [95] or synthetic polymers [96].…”

Section: Key Macromoleculesmentioning

confidence: 99%

Molecular representations in AI-driven drug discovery: a review and practical guide

et al. 2020

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“…The heterogeneous roles of galectins in these physiological and pathophysiological processes have motivated the rational design of fine-tuned inhibitors with precise selectivity and specificity. The characterization at the molecular level of the interaction of galectins with their natural binders has provided the structural basis for the design of potent antagonists (Ardá and Jiménez-Barbero, 2018 ; Valverde et al, 2019a ).…”

Section: Introductionmentioning

confidence: 99%

Targeting Galectins With Glycomimetics

et al. 2020

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Among glycan-binding proteins, galectins, β-galactoside-binding lectins, exhibit relevant biological roles and are implicated in many diseases, such as cancer and inflammation. Their involvement in crucial pathologies makes them interesting targets for drug discovery. In this review, we gather the last approaches toward the specific design of glycomimetics as potential drugs against galectins. Different approaches, either using specific glycomimetic molecules decorated with key functional groups or employing multivalent presentations of lactose and N-acetyl lactosamine analogs, have provided promising results for binding and modulating different galectins. The review highlights the results obtained with these approximations, from the employment of S-glycosyl compounds to peptidomimetics and multivalent glycopolymers, mostly employed to recognize and/or detect h Gal-1 and h Gal-3.

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“…Different types of strategies were used to design selectin antagonists, including carbohydrates, glycomimetics, non-carbohydrate small molecules, macromolecules, peptides, monoclonal antibodies, and DNA-aptamers. These efforts were reviewed recently [11,20,256,304,305,[318][319][320][321][322][323][324].…”

Section: Glycomimetic Inhibitorsmentioning

confidence: 99%

Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review

2020

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Selectins belong to a group of adhesion molecules that fulfill an essential role in immune and inflammatory responses and tissue healing. Selectins are glycoproteins that decode the information carried by glycan structures, and non-covalent interactions of selectins with these glycan structures mediate biological processes. The sialylated and fucosylated tetrasaccharide sLex is an essential glycan recognized by selectins. Several glycosyltransferases are responsible for the biosynthesis of the sLex tetrasaccharide. Selectins are involved in a sequence of interactions of circulated leukocytes with endothelial cells in the blood called the adhesion cascade. Recently, it has become evident that cancer cells utilize a similar adhesion cascade to promote metastases. However, like Dr. Jekyll and Mr. Hyde’s two faces, selectins also contribute to tissue destruction during some infections and inflammatory diseases. The most prominent function of selectins is associated with the initial stage of the leukocyte adhesion cascade, in which selectin binding enables tethering and rolling. The first adhesive event occurs through specific non-covalent interactions between selectins and their ligands, with glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains a principal strategy aimed at developing new therapies for the treatment of immune and inflammatory disorders and cancer. In this review, we will survey the significant contributions to and the current status of the understanding of the structure of selectins and the role of selectins in various biological processes. The potential of selectins and their ligands as therapeutic targets in chronic and acute inflammatory diseases and cancer will also be discussed. We will emphasize the structural characteristic of selectins and the catalytic mechanisms of glycosyltransferases involved in the biosynthesis of glycan recognition determinants. Furthermore, recent achievements in the synthesis of selectin inhibitors will be reviewed with a focus on the various strategies used for the development of glycosyltransferase inhibitors, including substrate analog inhibitors and transition state analog inhibitors, which are based on knowledge of the catalytic mechanism.

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Glycans in drug discovery

Abstract: Exploiting glycan recognition in drug discovery.

Cited by 73 publications

References 170 publications

Molecular representations in AI-driven drug discovery: a review and practical guide

Molecular representations in AI-driven drug discovery: a review and practical guide

Targeting Galectins With Glycomimetics

Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review

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