Reactivity of anti-HNK-1 antibodies to branched O- mannose glycans associated with demyelination

Sakuda, Kanoko; Kizuka, Yasuhiko; Yamaguchi, Yoshiki; Tanaka, Katsunori; Ogiwara, Ken; Segawa, Tatsuya; Hagiwara, Yoshihiro; Matsuo, Ichiro; Ogawa, Haruko; Taniguchi, Naoyuki; Kitazume, Shinobu

doi:10.1016/j.bbrc.2017.04.085

Cited by 13 publications

(16 citation statements)

References 32 publications

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“…Previous chemical synthesis of HNK-1-containing paragloboside pentasaccharide (SGPG, II ) required tedious protecting group manipulation of judiciously designed orthogonal protecting groups for site-specific sulfation as well as stereo- and regioselective glycosylation. ,, These chemical approaches also suffered from low reactivity of GlcA donors, , making it unsuitable for the synthesis of HNK-1-containing complex glycans. Most recently, the use of a recombinant human HNK-1 sulfotransferase (HNK-1ST) was attempted for enzymatic sulfation of the terminal GlcA unit in the synthesis of a C2,C6-branched O -mannose glycan . However, the sulfation reaction did not go to completion presumably due to the low catalytic efficiency of HNK-1ST; thus the products with different sulfation patterns had to be purified by HPLC and were characterized only by LC–MS …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Most recently, the use of a recombinant human HNK-1 sulfotransferase (HNK-1ST) was attempted for enzymatic sulfation of the terminal GlcA unit in the synthesis of a C2,C6-branched O-mannose glycan. 13 However, the sulfation reaction did not go to completion presumably due to the low catalytic efficiency of HNK-1ST; thus the products with different sulfation patterns had to be purified by HPLC and were characterized only by LC−MS. 13 It is well-known that glucuronoside undergoes 6,3lactonization under peracetylation condition, which provides an easy access to free C3-OH at glucuropyranoside for further modification after methanolysis.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Chemoenzymatic Synthesis of O-Mannose Glycans Containing Sulfated or Nonsulfated HNK-1 Epitope

et al. 2019

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The human natural killer-1 (HNK-1) epitope is a unique sulfated trisaccharide sequence presented on O-and N-glycans of various glycoproteins and on glycolipids. It is overexpressed in the nervous system and plays crucial roles in nerve regeneration, synaptic plasticity, and neuronal diseases. However, the investigation of functional roles of HNK-1 in a more complex glycan context at the molecular level remains a big challenge due to lack of access to related structurally welldefined complex glycans. Herein, we describe a highly efficient chemoenzymatic approach for the first collective synthesis of HNK-1-bearing O-mannose glycans with different branching patterns, and for their nonsulfated counterparts. The successful strategy relies on both chemical glycosylation of a trisaccharide lactone donor for the introduction of sulfated HNK-1 branch and substrate promiscuities of bacterial glycosyltransferases that can tolerate sulfated substrates for enzymatic diversification. Glycan microarray analysis with the resulting complex synthetic glycans demonstrated their recognition by two HNK-1-specific antibodies including anti-HNK-1/ N-CAM (CD57) and Cat-315, which provided further evidence for the recognition epitopes of these antibodies and the essential roles of the sulfate group for HNK-1 glycan-antibody recognition.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

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Chemoenzymatic Synthesis of O-Mannose Glycans Containing Sulfated or Nonsulfated HNK-1 Epitope

et al. 2019

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“…On the other hand, an anti-PTPRZ antibody showed a coarser staining pattern in the corpus callosum with cuprizone feeding, whereas the mean staining intensity did not significantly differ statistically ( S5 Fig ). The expression of PTPRZ was previously shown to be increased by cuprizone feeding [ 49 , 50 ]; therefore, we also examined the mRNA expression of Ptprz . A quantitative PCR analysis of paraffin sections of the cortex including the corpus callosum showed that its mRNA expression was significantly increased ( S5 Fig ).…”

Section: Resultsmentioning

confidence: 99%

Protamine neutralizes chondroitin sulfate proteoglycan-mediated inhibition of oligodendrocyte differentiation

et al. 2017

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Chondroitin sulfate proteoglycans (CSPGs), which are enriched in demyelinating plaques in neurodegenerative diseases, such as multiple sclerosis (MS), impair remyelination by inhibiting the migration and differentiation of oligodendrocyte precursor cells (OPCs) in the central nervous system (CNS). We herein show that protamine (PRM, also known as a heparin antagonist) effectively neutralizes the inhibitory activities of CSPGs, thereby enhancing OPC differentiation and (re)myelination in mice. Cell-based assays using mouse OPC-like OL1 cells revealed that the PRM treatment exerted masking effects on extracellular CSPGs and improved oligodendrocyte differentiation on inhibitory CSPG-coated substrates. PRM also bound to the extracellular region of protein tyrosine phosphatase receptor type Z (PTPRZ), a membrane-spanning CSPG predominantly expressed in OPCs, and functioned as a ligand mimetic of PTPRZ, thereby suppressing its negative regulatory activity on oligodendrocyte differentiation. In primary cultures, the differentiation of OPCs from wild-type and Ptprz-deficient mice was equally enhanced by PRM. Moreover, the intranasal administration of PRM accelerated myelination in the developing mouse brain, and its intracerebroventricular administration stimulated remyelination after cuprizone-induced demyelination. These results indicate that PRM has CSPG-neutralizing activity which promotes oligodendrocyte differentiation under developmental and morbid conditions.

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“…Expression of O-glycans has been investigated in samples from patients with MS, AD, and HD and/or models of these diseases [28][29][30][31]. Preliminary assessment of the involvement of O-glycans in MS was reported by Sakuda et al, who showed that demyelination leads to upregulation of the expression of human natural killer 1 carbohydrate (HNK-1) on O-mannosyl glycans, which is associated with high immunogenicity and potentially increased inflammation [29]. O-mannosyl glycans (the branched formation of which is catalysed by N-acetylglucosaminyltransferase-IX) have previously been reported to inhibit remyelination [30].…”

Section: Open Accessmentioning

confidence: 99%

Role and therapeutic implications of protein glycosylation in neuroinflammation

Rebelo

Chevalier

Russo

et al. 2022

Trends in Molecular Medicine

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Reactivity of anti-HNK-1 antibodies to branched O- mannose glycans associated with demyelination

Cited by 13 publications

References 32 publications

Chemoenzymatic Synthesis of O-Mannose Glycans Containing Sulfated or Nonsulfated HNK-1 Epitope

Chemoenzymatic Synthesis of O-Mannose Glycans Containing Sulfated or Nonsulfated HNK-1 Epitope

Protamine neutralizes chondroitin sulfate proteoglycan-mediated inhibition of oligodendrocyte differentiation

Role and therapeutic implications of protein glycosylation in neuroinflammation

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