E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Glycomimetics: Design, Synthesis and Therapeutic Applications"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: closed (30 January 2018)

Special Issue Editor

Guest Editor
Prof. Philippe Compain

École Européenne de Chimie, Polymères et Matériaux, Université de Strasbourg, Strasbourg, France
Website | E-Mail
Interests: organic synthesis; glycomimetics; synthetic methodologies; C-H functionalization; multivalency; enzyme inhibitors; carbohydrate-processing enzymes; rare genetic diseases

Special Issue Information

Dear Colleagues,

Glycomimetics, as structurally altered analogues of sugars, offer the opportunity to emulate carbohydrate activities while circumventing their drawbacks as credible drugs. Structural modifications are performed not only to enhance target affinity and selectivity but also to improve drug-like properties, including oral bioavailability and in vivo stability. Beyond their biological interest, glycomimetics are an amazing playground for organic chemists. Creatively imagining new chemical structures that compete with one of the most important classes of biomolecules is a strong driving force. To paraphrase Marcellin Berthelot, organic chemists are indeed always eager to create their own objects of study. The high density of functional groups and asymmetric centers present in carbohydrate structures provide a rich source of inspiration. Beyond rational thinking, a kind of quest for molecular beauty via simplicity or symmetry is part of the design process. With regards to synthetic methodologies, the relative structural complexity of glycomimetics also provides a formidable testing ground for known reactions while permitting accidental discoveries in synthesis. In this Special Issue we intend to collect reviews, original research articles and short communications covering all current aspects of glycomimetic chemistry from innovative synthesis to potential therapeutic applications. Original research works on iminosugars, C-glycosides, square sugars or other sweet objects are therefore welcome, whether these glycomimetics were designed for the synthetic challenges they provide, for tackling fundamental questions in glycobiology, or for drug discovery.

Prof. Dr. Philippe Compain
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glycomimetics
  • iminosugars
  • carbasugars
  • C-glycosides
  • thiosugars
  • multivalency
  • inhibitors
  • lectins
  • carbohydrate-processing enzymes
  • carbohydrate-mediated biological recognition

Published Papers (9 papers)

View options order results:
result details:
Displaying articles 1-9
Export citation of selected articles as:

Editorial

Jump to: Research, Review

Open AccessFeature PaperEditorial Glycomimetics: Design, Synthesis, and Therapeutic Applications
Molecules 2018, 23(7), 1658; https://doi.org/10.3390/molecules23071658
Received: 6 July 2018 / Accepted: 7 July 2018 / Published: 7 July 2018
PDF Full-text (163 KB) | HTML Full-text | XML Full-text
(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)

Research

Jump to: Editorial, Review

Open AccessArticle Probing the Inhibitor versus Chaperone Properties of sp2-Iminosugars towards Human β-Glucocerebrosidase: A Picomolar Chaperone for Gaucher Disease
Molecules 2018, 23(4), 927; https://doi.org/10.3390/molecules23040927
Received: 26 March 2018 / Revised: 26 March 2018 / Accepted: 12 April 2018 / Published: 17 April 2018
Cited by 1 | PDF Full-text (2327 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of sp2-iminosugar glycomimetics differing in the reducing or nonreducing character, the configurational pattern (d-gluco or l-ido), the architecture of the glycone skeleton, and the nature of the nonglycone substituent has been synthesized and
[...] Read more.
A series of sp2-iminosugar glycomimetics differing in the reducing or nonreducing character, the configurational pattern (d-gluco or l-ido), the architecture of the glycone skeleton, and the nature of the nonglycone substituent has been synthesized and assayed for their inhibition properties towards commercial glycosidases. On the basis of their affinity and selectivity towards GH1 β-glucosidases, reducing and nonreducing bicyclic derivatives having a hydroxylation profile of structural complementarity with d-glucose and incorporating an N′-octyl-isourea or -isothiourea segment were selected for further evaluation of their inhibitory/chaperoning potential against human glucocerebrosidase (GCase). The 1-deoxynojirimycin (DNJ)-related nonreducing conjugates behaved as stronger GCase inhibitors than the reducing counterparts and exhibited potent chaperoning capabilities in Gaucher fibroblasts hosting the neuronopathic G188S/G183W mutation, the isothiourea derivative being indeed one of the most efficient chaperone candidates reported up to date (70% activity enhancement at 20 pM). At their optimal concentration, the four selected compounds promoted mutant GCase activity enhancements over 3-fold; yet, the inhibitor/chaperoning balance became unfavorable at much lower concentration for nonreducing as compared to reducing derivatives. Full article
(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)
Figures

Graphical abstract

Open AccessFeature PaperCommunication One-Pot, Highly Stereoselective Synthesis of Dithioacetal-α,α-Diglycosides
Molecules 2018, 23(4), 914; https://doi.org/10.3390/molecules23040914
Received: 28 March 2018 / Revised: 12 April 2018 / Accepted: 13 April 2018 / Published: 15 April 2018
Cited by 3 | PDF Full-text (1157 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A one-step access to dithioacetal-α,α-diglycosides is reported. The synthetic strategy is based on the thioacetalization of aldehydes or ketones via highly stereoselective ring-opening of 1,6 anhydrosugars with bis(trimethylsilyl)sulfide. Full article
(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)
Figures

Graphical abstract

Open AccessFeature PaperArticle Potent GH20 N-Acetyl-β-d-hexosaminidase Inhibitors: N-Substituted 3-acetamido-4-amino-5-hydroxymethyl-cyclopentanediols
Molecules 2018, 23(3), 708; https://doi.org/10.3390/molecules23030708
Received: 28 February 2018 / Revised: 15 March 2018 / Accepted: 16 March 2018 / Published: 20 March 2018
Cited by 1 | PDF Full-text (2403 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
From 1,2;3,4-di-O-isopropylidene-d-galactopyranose, a preliminary series of highly functionalized amino(hydroxymethyl)cyclopentanes was easily available. These amine-containing basic carbasugars featuring the d-galacto configuration are potent inhibitors of the GH20 β-d-hexosaminidases probed and may bear potential as regulators of
[...] Read more.
From 1,2;3,4-di-O-isopropylidene-d-galactopyranose, a preliminary series of highly functionalized amino(hydroxymethyl)cyclopentanes was easily available. These amine-containing basic carbasugars featuring the d-galacto configuration are potent inhibitors of the GH20 β-d-hexosaminidases probed and may bear potential as regulators of N-acetyl-d-hexosaminidase activities in vivo. Full article
(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)
Figures

Graphical abstract

Open AccessFeature PaperArticle Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase
Molecules 2018, 23(3), 666; https://doi.org/10.3390/molecules23030666
Received: 27 February 2018 / Revised: 7 March 2018 / Accepted: 13 March 2018 / Published: 15 March 2018
Cited by 2 | PDF Full-text (6665 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the present study was to broaden the structure-activity relationships of C- and N-β-d-glucopyranosyl azole type inhibitors of glycogen phosphorylase. 1-Aryl-4-β-d-gluco-pyranosyl-1,2,3-triazoles were prepared by copper catalyzed azide-alkyne cycloadditions between O-perbenzylated or O-peracetylated β-
[...] Read more.
The aim of the present study was to broaden the structure-activity relationships of C- and N-β-d-glucopyranosyl azole type inhibitors of glycogen phosphorylase. 1-Aryl-4-β-d-gluco-pyranosyl-1,2,3-triazoles were prepared by copper catalyzed azide-alkyne cycloadditions between O-perbenzylated or O-peracetylated β-d-glucopyranosyl ethynes and aryl azides. 1-β-d-Gluco-pyranosyl-4-phenyl imidazole was obtained in a glycosylation of 4(5)-phenylimidazole with O-peracetylated α-d-glucopyranosyl bromide. C-β-d-Glucopyranosyl-N-substituted-tetrazoles were synthesized by alkylation/arylation of O-perbenzoylated 5-β-d-glucopyranosyl-tetrazole or from a 2,6-anhydroheptose tosylhydrazone and arenediazonium salts. 5-Substituted tetrazoles were glycosylated by O-peracetylated α-d-glucopyranosyl bromide to give N-β-d-glucopyranosyl-C-substituted-tetrazoles. Standard deprotections gave test compounds which were assayed against rabbit muscle glycogen phosphorylase b. Most of the compounds proved inactive, the best inhibitor was 2-β-d-glucopyranosyl-5-phenyltetrazole (IC50 600 μM). These studies extended the structure-activity relationships of β-d-glucopyranosyl azole type inhibitors and revealed the extreme sensitivity of such type of inhibitors towards the structure of the azole moiety. Full article
(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)
Figures

Graphical abstract

Open AccessFeature PaperCommunication Convergent Synthesis of N,S-bis Glycosylquinolin-2-ones via a Pd-G3-XantPhos Precatalyst Catalysis
Molecules 2018, 23(3), 519; https://doi.org/10.3390/molecules23030519
Received: 29 January 2018 / Revised: 8 February 2018 / Accepted: 10 February 2018 / Published: 26 February 2018
Cited by 2 | PDF Full-text (1354 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Buchwald-Hartwig-Migita cross-coupling of 1-thiosugars with α- or β-3-iodo-N-glycosylquinolin-2-ones has been accomplished under mild and operationally simple reaction conditions through the use of a Pd-G3 XantPhos palladacycle precatalyst. This new methodology has been successfully applied to a variety of α- or β-mono-,
[...] Read more.
Buchwald-Hartwig-Migita cross-coupling of 1-thiosugars with α- or β-3-iodo-N-glycosylquinolin-2-ones has been accomplished under mild and operationally simple reaction conditions through the use of a Pd-G3 XantPhos palladacycle precatalyst. This new methodology has been successfully applied to a variety of α- or β-mono-, di-, and poly-thiosugar derivatives to efficiently synthesize a series of α- or β-N,S-bis-glycosyl quinolin-2-ones, which are difficult to synthesize by classical methods. Full article
(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)
Figures

Graphical abstract

Open AccessFeature PaperArticle Probing the Influence of Linker Length and Flexibility in the Design and Synthesis of New Trehalase Inhibitors
Molecules 2018, 23(2), 436; https://doi.org/10.3390/molecules23020436
Received: 30 January 2018 / Revised: 12 February 2018 / Accepted: 14 February 2018 / Published: 16 February 2018
Cited by 3 | PDF Full-text (3034 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This work aims to synthesize new trehalase inhibitors selective towards the insect trehalase versus the porcine trehalase, in view of their application as potentially non-toxic insecticides and fungicides. The synthesis of a new pseudodisaccharide mimetic 8, by means of a stereoselective α-glucosylation
[...] Read more.
This work aims to synthesize new trehalase inhibitors selective towards the insect trehalase versus the porcine trehalase, in view of their application as potentially non-toxic insecticides and fungicides. The synthesis of a new pseudodisaccharide mimetic 8, by means of a stereoselective α-glucosylation of the key pyrrolizidine intermediate 13, was accomplished. The activity of compound 8 as trehalase inhibitor towards C. riparius trehalase was evaluated and the results showed that 8 was active in the μM range and showed a good selectivity towards the insect trehalase. To reduce the overall number of synthetic steps, simpler and more flexible disaccharide mimetics 911 bearing a pyrrolidine nucleus instead of the pyrrolizidine core were synthesized. The biological data showed the key role of the linker chain’s length in inducing inhibitory properties, since only compounds 9 (α,β-mixture), bearing a two-carbon atom linker chain, maintained activity as trehalase inhibitors. A proper change in the glucosyl donor-protecting groups allowed the stereoselective synthesis of the β-glucoside 9β, which was active in the low micromolar range (IC50 = 0.78 μM) and 12-fold more potent (and more selective) than 9α towards the insect trehalase. Full article
(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)
Figures

Graphical abstract

Review

Jump to: Editorial, Research

Open AccessFeature PaperReview Glycoside Mimics from Glycosylamines: Recent Progress
Molecules 2018, 23(7), 1612; https://doi.org/10.3390/molecules23071612
Received: 31 May 2018 / Revised: 26 June 2018 / Accepted: 28 June 2018 / Published: 2 July 2018
Cited by 1 | PDF Full-text (13466 KB) | HTML Full-text | XML Full-text
Abstract
Glycosylamines are valuable sugar derivatives that have attracted much attention as synthetic intermediates en route to iminosugar-C-glycosyl compounds. Iminosugars are among the most important glycomimetics reported to date due to their powerful activities as inhibitors of a wide variety of glycosidases
[...] Read more.
Glycosylamines are valuable sugar derivatives that have attracted much attention as synthetic intermediates en route to iminosugar-C-glycosyl compounds. Iminosugars are among the most important glycomimetics reported to date due to their powerful activities as inhibitors of a wide variety of glycosidases and glycosyltransferases, as well as for their use as pharmacological chaperones. As they provide ready access to these important glycoside mimics, we have reviewed the most significant glycosylamine-based methodologies developed to date, with a special emphasis on the literature reported after 2006. The groups of substrates covered include N-alkyl- and N-benzyl-glycosylamines, N-glycosylhydroxylamines, N-(alkoxycarbonyl)-, and N-tert-butanesulfinyl-glycosylamines. Full article
(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)
Figures

Graphical abstract

Open AccessReview Synthesis of O-Amino Sugars and Nucleosides
Molecules 2018, 23(3), 641; https://doi.org/10.3390/molecules23030641
Received: 25 January 2018 / Revised: 26 February 2018 / Accepted: 9 March 2018 / Published: 12 March 2018
Cited by 1 | PDF Full-text (3723 KB) | HTML Full-text | XML Full-text
Abstract
Nucleic acids and carbohydrates are essential biomolecules involved in numerous biological and pathological processes. Development of multifunctional building blocks based on nucleosides and sugars is in high demand for the generation of novel oligonucleotide mimics and glycoconjugates for biomedical applications. Recently, aminooxyl-functionalized compounds
[...] Read more.
Nucleic acids and carbohydrates are essential biomolecules involved in numerous biological and pathological processes. Development of multifunctional building blocks based on nucleosides and sugars is in high demand for the generation of novel oligonucleotide mimics and glycoconjugates for biomedical applications. Recently, aminooxyl-functionalized compounds have attracted increasing research interest because of their easy derivatization through oxime ligation or N-oxyamide formation reactions. Various biological applications have been reported for O-amino carbohydrate- and nucleoside-derived compounds. Here, we report our efforts in the design and synthesis of glyco-, glycosyl, nucleoside- and nucleo-aminooxy acid derivatives from readily available sugars and amino acids, and their use for the generation of N-oxyamide-linked oligosaccharides, glycopeptides, glycolipids, oligonucleosides and nucleopeptides as novel glycoconjugates or oligonucleotide mimics. Delicate and key points in the synthesis will be emphasized. Full article
(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)
Figures

Graphical abstract

Back to Top