Special Issue "Carbohydrates 2018"

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (15 March 2019)

Special Issue Editors

Guest Editor
Prof. Dr. Amélia Pilar Rauter

Departamento de Química e Bioquímica (DQB) e Centro de Química e Bioquímica (CQB), Faculdade de Ciências, Universidade de Lisboa (FCUL), Rua Ernesto de Vasconcelos, Campo Grande,Edifício C8, 5º Piso, 1749-016 Lisboa, Portugal
Website | E-Mail
Interests: carbohydrate small molecule synthesis; organic and biomolecular chemistry developments towards new therapeutic approaches for diabetes; Alzheimer’s disease and other amyloid diseases and carbohydrate-based antibiotics
Guest Editor
Dr. Nuno Manuel Xavier

Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Ed. C8, 2º Piso, Campo Grande, 1749-016 Lisboa, Portugal
Website | E-Mail
Interests: carbohydrates; nucleos(t)ides; cancer; enzyme inhibitors

Special Issue Information

Dear Colleagues,

Carbohydrates play a major role in a diversity of processes, which are encompassed in the areas of chemistry, biochemistry, biology and medicinal chemistry. Among the topics covered at the 29th International Carbohydrate Symposium (ICS2018), special attention is given to recent advances and emerging trends in carbohydrate research towards medical applications, including carbohydrates in therapeutics and diagnosis, glycosylation and disease, carbohydrates in inflammation and disease, glycosciences and personalized medicine and carbohydrate vaccines. The growing knowledge on the importance of carbohydrates in health and in disease progress, driving new therapeutic strategies, is the motto for this Special Issue. Contributions arising from the presentations at the Symposium within the context of the previously mentioned topics are welcome.

Speakers at the symposium are cordially invited to submit original research manuscripts to this Special Issue of Pharmaceuticals.

Prof. Dr. Amélia Pilar Rauter
Dr. Nuno Manuel Xavier
Guest Editors

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. Pharmaceuticals is an international peer-reviewed open access quarterly 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 850 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

  • glycosylation-related diseases/disorders
  • disease-associated carbohydrate-processing enzymes
  • carbohydrate-based therapeutics
  • carbohydrate-based lead molecules
  • medicinal glycochemistry

Published Papers (5 papers)

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Research

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Open AccessArticle Chain-Branched Polyhydroxylated Octahydro-1H-Indoles as Potential Leads against Lysosomal Storage Diseases
Pharmaceuticals 2019, 12(2), 47; https://doi.org/10.3390/ph12020047
Received: 13 February 2019 / Revised: 15 March 2019 / Accepted: 19 March 2019 / Published: 29 March 2019
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Abstract
Here, the synthesis and glycosidase inhibition properties of the two first known 3-ethyloctahydro-1H-indole-4,5,6-triols are reported. This study shows the transformation of d-glucose into polyhydroxylated 1-(2-nitrocyclohexane) acetaldehydes, followed by a protocol involving the formation of the azacyclopentane ring. Results of inhibitory [...] Read more.
Here, the synthesis and glycosidase inhibition properties of the two first known 3-ethyloctahydro-1H-indole-4,5,6-triols are reported. This study shows the transformation of d-glucose into polyhydroxylated 1-(2-nitrocyclohexane) acetaldehydes, followed by a protocol involving the formation of the azacyclopentane ring. Results of inhibitory potency assays and docking calculations show that at least one of them could be a lead for optimization in the search for compounds that behave like folding chaperones in lysosomal storage diseases. Full article
(This article belongs to the Special Issue Carbohydrates 2018)
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Open AccessCommunication Development of a Microwave-assisted Chemoselective Synthesis of Oxime-linked Sugar Linkers and Trivalent Glycoclusters
Pharmaceuticals 2019, 12(1), 39; https://doi.org/10.3390/ph12010039
Received: 19 February 2019 / Revised: 5 March 2019 / Accepted: 8 March 2019 / Published: 14 March 2019
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Abstract
A rapid, high-yielding microwave-mediated synthetic procedure was developed and optimized using a model system of monovalent sugar linkers, with the ultimate goal of using this method for the synthesis of multivalent glycoclusters. The reaction occurs between the aldehyde/ketone on the sugars and an [...] Read more.
A rapid, high-yielding microwave-mediated synthetic procedure was developed and optimized using a model system of monovalent sugar linkers, with the ultimate goal of using this method for the synthesis of multivalent glycoclusters. The reaction occurs between the aldehyde/ketone on the sugars and an aminooxy moiety on the linker/trivalent core molecules used in this study, yielding acid-stable oxime linkages in the products and was carried out using equimolar quantities of reactants under mild aqueous conditions. Because the reaction is chemoselective, sugars can be incorporated without the use of protecting groups and the reactions can be completed in as little as 30 min in the microwave. As an added advantage, in the synthesis of the trivalent glycoclusters, the fully substituted trivalent molecules were the major products produced in excellent yields. These results illustrate the potential of this rapid oxime-forming microwave-mediated reaction in the synthesis of larger, more complex glycoconjugates and glycoclusters for use in a wide variety of biomedical applications. Full article
(This article belongs to the Special Issue Carbohydrates 2018)
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Open AccessArticle Development and Characterization of Chitosan Microparticles-in-Films for Buccal Delivery of Bioactive Peptides
Pharmaceuticals 2019, 12(1), 32; https://doi.org/10.3390/ph12010032
Received: 17 January 2019 / Revised: 5 February 2019 / Accepted: 11 February 2019 / Published: 20 February 2019
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Abstract
Nowadays, bioactive peptides are used for therapeutic applications and the selection of a carrier to deliver them is very important to increase the efficiency, absorption, release, bioavailability and consumer acceptance. The aim of this study was to develop and characterize chitosan-based films loaded [...] Read more.
Nowadays, bioactive peptides are used for therapeutic applications and the selection of a carrier to deliver them is very important to increase the efficiency, absorption, release, bioavailability and consumer acceptance. The aim of this study was to develop and characterize chitosan-based films loaded with chitosan microparticles containing a bioactive peptide (sequence: KGYGGVSLPEW) with antihypertensive properties. Films were prepared by the solvent casting method, while the microparticles were prepared by ionic gelation. The final optimized chitosan microparticles exhibited a mean diameter of 2.5 µm, a polydispersity index of 0.46, a zeta potential of +61 mV and a peptide association efficiency of 76%. Chitosan films were optimized achieving the final formulation of 0.79% (w/v) of chitosan, 6.74% (w/v) of sorbitol and 0.82% (w/v) of citric acid. These thin (±0.100 mm) and transparent films demonstrated good performance in terms of mechanical and biological properties. The oral films developed were flexible, elastic, easy to handle and exhibited rapid disintegration (30 s) and an erosion behavior of 20% when they came into contact with saliva solution. The cell viability (75–99%) was proved by methylthiazolydiphenyl-tetrazolium bromide (MTT) assay with TR146 cells. The chitosan mucoadhesive films loaded with peptide–chitosan microparticles resulted in an innovative approach to perform administration across the buccal mucosa, because these films present a larger surface area, leading to the rapid disintegration and release of the antihypertensive peptide under controlled conditions in the buccal cavity, thus promoting bioavailability. Full article
(This article belongs to the Special Issue Carbohydrates 2018)
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Open AccessArticle Conformation and Cross-Protection in Group B Streptococcus Serotype III and Streptococcus pneumoniae Serotype 14: A Molecular Modeling Study
Pharmaceuticals 2019, 12(1), 28; https://doi.org/10.3390/ph12010028
Received: 19 January 2019 / Revised: 1 February 2019 / Accepted: 9 February 2019 / Published: 13 February 2019
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Abstract
Although the branched capsular polysaccharides of Streptococcus agalactiae serotype III (GBSIII PS) and Streptococcus pneumoniae serotype 14 (Pn14 PS) differ only in the addition of a terminal sialic acid on the GBSIII PS side chains, these very similar polysaccharides are immunogenically distinct. Our [...] Read more.
Although the branched capsular polysaccharides of Streptococcus agalactiae serotype III (GBSIII PS) and Streptococcus pneumoniae serotype 14 (Pn14 PS) differ only in the addition of a terminal sialic acid on the GBSIII PS side chains, these very similar polysaccharides are immunogenically distinct. Our simulations of GBSIII PS, Pn14 PS and the unbranched backbone polysaccharide provide a conformational rationale for the different antigenic epitopes identified for these PS. We find that side chains stabilize the proximal β dGlc(1→6) β dGlcNAc backbone linkage, restricting rotation and creating a well-defined conformational epitope at the branch point. This agrees with the glycotope structure recognized by an anti-GBSIII PS functional monoclonal antibody. We find the same dominant solution conformation for GBSIII and Pn14 PS: aside from the branch point, the backbone is very flexible with a “zig-zag” conformational habit, rather than the helix previously proposed for GBSIII PS. This suggests a common strategy for bacterial evasion of the host immune system: a flexible backbone that is less perceptible to the immune system, combined with conformationally-defined branch points presenting human-mimic epitopes. This work demonstrates how small structural features such as side chains can alter the conformation of a polysaccharide by restricting rotation around backbone linkages. Full article
(This article belongs to the Special Issue Carbohydrates 2018)
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Review

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Open AccessReview Strategies for the Development of Glycomimetic Drug Candidates
Pharmaceuticals 2019, 12(2), 55; https://doi.org/10.3390/ph12020055
Received: 15 March 2019 / Revised: 3 April 2019 / Accepted: 9 April 2019 / Published: 11 April 2019
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Abstract
Carbohydrates are a structurally-diverse group of natural products which play an important role in numerous biological processes, including immune regulation, infection, and cancer metastasis. Many diseases have been correlated with changes in the composition of cell-surface glycans, highlighting their potential as a therapeutic [...] Read more.
Carbohydrates are a structurally-diverse group of natural products which play an important role in numerous biological processes, including immune regulation, infection, and cancer metastasis. Many diseases have been correlated with changes in the composition of cell-surface glycans, highlighting their potential as a therapeutic target. Unfortunately, native carbohydrates suffer from inherently weak binding affinities and poor pharmacokinetic properties. To enhance their usefulness as drug candidates, ‘glycomimetics’ have been developed: more drug-like compounds which mimic the structure and function of native carbohydrates. Approaches to improve binding affinities (e.g., deoxygenation, pre-organization) and pharmacokinetic properties (e.g., limiting metabolic degradation, improving permeability) have been highlighted in this review, accompanied by relevant examples. By utilizing these strategies, high-affinity ligands with optimized properties can be rationally designed and used to address therapies for novel carbohydrate-binding targets. Full article
(This article belongs to the Special Issue Carbohydrates 2018)
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