Synthesis of Disaccharides Containing 6-Deoxy-a-L-talose as Potential Heparan Sulfate Mimetics

Fairweather, Jon K.; Liu, Ligong; Karoli, Tomislav; Ferro, Vito

doi:10.3390/molecules17089790

Cited by 10 publications

(8 citation statements)

References 38 publications

(44 reference statements)

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“…222 FGF-2 affinity-purified HS for enhanced expansion of stem cells, 223 a trisulfated HS RANTES antagonist, 224 IFN-γ-binding HS, 225,226 AT-binding HS pentasaccharides, 227 and VEGF affinity-purified HS 228 for an improved vascular repair. HS biomimetics based on 6-deoxy-α-talose, 229 OTR4120 mimetic HS 230 for an improved cutaneous wound repair, and HS biomimetic clusters 231 have been developed. The heparinoid pentosan polysulfate has found application in IVD 232,233 and cartilage repair and in combination with MSCs and spinal interbody cages 234 for spinal fusions.…”

Section: Introductionmentioning

confidence: 99%

Glycosaminoglycans in Wound Healing

Melrose

2016

Bone�Tissue�Regen�Insights

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ABSTR ACT: Glycosaminoglycans (GAGs) are ancient molecules that have persisted throughout vertebrate and invertebrate evolution for many hundreds of millions of years. They have essential roles in the regulation of many fundamental physiological processes, which control cellular proliferation, differentiation, matrix assembly, homeostasis, and cellular behavior, which has ensured the survival of vertebrates and invertebrates to the present day. In this study, we review the roles of GAGs in wound repair in a number of tissues. The healing of some wounds such as diabetic ulcers, cartilaginous defects, and damaged neural tissue can be a particularly demanding clinical problem. However, with the directive roles that GAGs have established through evolution, the development of key matrix and cellular molecules to control cellular behavior has resulted in the development of sophisticated control systems to regulate key physiological life-preserving processes. The control of wound repair is but one example of these. With a greater understanding of how GAGs actually do this, inroads are being made in the application of this information in the development of therapeutic procedures to improve repair of these problematic tissues. The application of engineered heparin sulfate (HS), human natural killer-1 (HNK-1), and HS biomimetics in neuromuscular repair biology, activated protein C in the treatment of diabetic ulcers, and affinity-isolated HS subfractions for specific applications in bone and vascular repair and in the improved expansion of mesenchymal stem cells for therapeutic applications represent significant advances in wound repair biology and emphasize the importance of GAGs in these processes. Armed with a greater understanding of the glycocode and the roles of GAGs in such repair processes, further improvements in therapeutic interventions are likely in the area of repair biology.

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Section: Introductionmentioning

confidence: 99%

Glycosaminoglycans in Wound Healing

Melrose

2016

Bone�Tissue�Regen�Insights

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“…Trituration with diethylether and recrystallization afforded targeted compound 5 in 32% yield as a white solid. The O ‐deacetyl glucosamine carboxamide 6 was obtained according to zemplén procedure (Fairweather, Liu, Karoli, & Ferro, ), via the reaction of compound 6 with sodium methoxide in methanol. TLC confirmed the end of the deprotection process using ninhydrin solution as a TLC visualizing reagent.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis, and biological evaluation of 1,8‐naphthyridine glucosamine conjugates as antimicrobial agents

Mohammed

Suaifan

Shehadeh

et al. 2018

Drug Development Research

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In the quest for discovering potent antimicrobial agents with lower toxicity, we envisioned the design and synthesis of nalidixic acid‐D‐(+)‐glucosamine conjugates. The novel compounds were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive bacteria, Gram negative bacteria and fungi. Cytotoxicity using MTT assay over L6 skeletal myoblast cell line, ATCC CRL‐1458 was carried out. In vitro antimicrobial assay revealed that 1‐ethyl‐7‐methyl‐4‐oxo‐N‐(1,3,4,6‐tetra‐O‐acetyl‐2‐deoxy‐D‐glucopyranose‐2‐yl)‐[1,8]‐naphthyridine‐3‐carboxamide (5) and 1‐ethyl‐7‐methyl‐4‐oxo‐N‐(2‐deoxy‐D‐glucopyranose‐2‐yl)‐[1,8]‐naphthyridine‐3‐carboxamide(6) possess growth inhibitory activity against resistant Escherichia coli NCTC, 11954 (MIC 0.1589 mM) and Methicillin resistant Staphylococcus aureus ATCC, 33591 (MIC 0.1589 mM). Compound (5) was more active against Listeria monocytogenes ATCC 19115 (MIC 0.1113 mM) in comparison with the reference nalidixic acid (MIC 1.0765 mM). Interestingly, compound (6) had potential antifungal activity against Candida albicans ATCC 10231 (MIC <0.0099 mM). Remarkably, the tested compounds had low cytotoxic effect. This study indicated that glucosamine moiety inclusion into the chemical structure of the marketed nalidixic acid enhances antimicrobial activity and safety.

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“…The other regioisomer was not detected. Then the Lev group was removed using hydrazine acetate, the resulting alcohol oxidized with Dess–Martin periodinane in refluxing DCE 56 , and the ketone reduced in the presence of NaBH 4 with full control of diastereoselectivity 57 . Attempts were made to protect the axial C4 position with a Lev group, yet, even under drastic conditions, only small amounts of the levulinoylated derivative were formed.…”

Section: Resultsmentioning

confidence: 99%

Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens

et al. 2017

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Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents of melioidosis and glanders, respectively, cause severe disease in both humans and animals. Studies have highlighted the importance of Bp and Bm lipopolysaccharides (LPS) as vaccine candidates. Here we describe the synthesis of seven oligosaccharides as the minimal structures featuring all of the reported acetylation/methylation patterns associated with Bp and Bm LPS O-antigens (OAgs). Our approach is based on the conversion of an l-rhamnose into a 6-deoxy-l-talose residue at a late stage of the synthetic sequence. Using biochemical and biophysical methods, we demonstrate the binding of several Bp and Bm LPS-specific monoclonal antibodies with terminal OAg residues. Mice immunized with terminal disaccharide–CRM197 constructs produced high-titer antibody responses that crossreacted with Bm-like OAgs. Collectively, these studies serve as foundation for the development of novel therapeutics, diagnostics, and vaccine candidates to combat diseases caused by Bp and Bm.

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Synthesis of Disaccharides Containing 6-Deoxy-a-L-talose as Potential Heparan Sulfate Mimetics

Cited by 10 publications

References 38 publications

Glycosaminoglycans in Wound Healing

Glycosaminoglycans in Wound Healing

Design, synthesis, and biological evaluation of 1,8‐naphthyridine glucosamine conjugates as antimicrobial agents

Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens

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