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Hironobu Hashimoto

Publications and source records attributed to Hironobu Hashimoto.

14 recordsLinked to original sources
PubMed2006

Exploitation of sugar ring flipping for a hinge-type tether assisting a [2 + 2] cycloaddition.

Methyl 3-O-p-methoxybenzyl-beta-D-xylopyranoside (2) was exploited as a novel hinge-type tether for the [2 + 2] cycloaddition of cinnamate. The major ring conformation occupied by the 2,4-dicinnamate derivative of 2 was 4C1, which extends two cinnamates along a diequatorial orientation. However, 3-O-deprotected dicinnamate 5, when in a non-polar solvent, favours the 1C4 conformation, which assists the approach of two cinnamates with the 1,3-diaxial scaffold. Photoirradiation of compound at 313 nm in CHCl3 afforded the intramolecular cycloaddition of cinnamates to give methyl beta-, delta-, and xi-truxinates in a 86 : 8 : 6 ratio after transesterification with methanol. The regio- and stereoselectivities are comparable to those reported by others for tethered cinnamates. The per-deuterated dicinnamate derivative of 5 facilitated the conformation analyses of the pyranoside rings by 1H NMR, indicating that all the products of photoirradiation had 1C4-fixed pyranosides. Excellent beta-selectivity was achieved when m-bromocinnamate was subjected to hinge-tethered [2 + 2] cycloaddition.

Carbohydrate Conformation↗
PubMed2005

Synthesis of bisubstrate analogues targeting alpha-1,3-fucosyltransferase and their activities.

We designed two bisubstrate analogues targeting alpha-1,3-fucosyltransferases, based on the three dimensional structure of Lewis X, which is the product of a alpha-1,3-fucosyltransferase reaction. We selected guanosine-5'-diphospho-L-galactose as a donor mimic and 2-hydroxyethyl beta-D-galactoside as an acceptor mimic, and tethered these two mimics with a methylene or ethylene linker. For the synthesis, the 6-position of L-galactose and the 6-position of D-galactose were first tethered via a methylene or ethylene linker. The L-galactose moiety was then converted to a GDP derivative. Both bisubstrate analogues were moderate inhibitors against alpha-1,3-fucosyltransferase V and VI. The fact that they were substrates of alpha-1,3-fucosyltransferase VI suggested that these compounds bound to the donor binding site, but not to the acceptor binding site.

Binding Sites↗
PubMed2005

An improvement in the bending ability of a hinged trisaccharide with the assistance of a sugar-sugar interaction.

Hinged di- and trisaccharides incorporating 2,4-diamino-beta-D-xylopyranoside as a hinge unit (Hin) were synthesized. Bridging of the diamino group of Hin by carbonylation or chelation to a metal ion results in a conformational change from (4)C1 to (1)C4, which in turn causes a bending of the oligosaccharides. In this study, the bending abilities of the hinged oligosaccharides were compared, in terms of the reactivities toward carbonylation and chelation. Di- or trisaccharides containing a 6-O-glycosylated mannopyranoside or galactopyranoside at their reducing ends had bending abilities similar to that of the Hin monosaccharide, probably because there were neither attractive nor repulsive interactions between the reducing and nonreducing ends. However, when Hin was attached at O2 of methyl mannopyranoside (Man alphaMe), the bending ability was dependent on the nonreducing sugar and the reaction conditions. Typically, a disaccharide--Hin beta(1,2)Man alphaMe--was difficult to bend under all the tested reaction conditions, and the bent population in the presence of Zn(II) was only 4%. On the other hand, a trisaccharide--Man alpha(1,3)Hin beta(1,2)Man alphaMe--was bent immediately after the addition of Zn(II) or Hg(II), and the bent population reached 75%, much larger than those of all the other hinged trisaccharides ever tested (<40%). This excellent bending ability suggests an attractive interaction between the reducing and nonreducing ends. The extended conformation was recovered by the addition of triethylenetetramine, a metal ion chelator. Reversible, quick, and efficient bending of the hinged trisaccharide was thus achieved.

Carbohydrate Conformation↗
PubMed2005

Synthesis of bisubstrate and donor analogues of sialyltransferase and their inhibitory activities.

[reaction: see text] Sialyltransferases (STs) are involved in the biosynthesis of glycoconjugates with important biological activities. Most STs utilize cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac) as a common donor substrate. A bisubstrate analogue containing the donor substrate (CMP-Neu5Ac mimic) and the acceptor substrate (galactose) was synthesized. Four donor analogues having the partial structure of the bisubstrate analogue were also synthesized to support study of the structure-activity relationship. Each analogue contains an ethylene group in place of the exocyclic anomeric oxygen of CMP-Neu5Ac. The bisubstrate analogue exhibited only weak inhibitory activity to rat recombinant alpha-2,3- and alpha-2,6-ST (IC(50) = 1.3, 2.4 mM). Conversion of the C-1 carboxylate of the Neu5Ac moiety to carboxyamide, hydroxymethyl, or methylene phosphate each resulted in a reduction in inhibitory activity. Among the synthesized analogues, cytidin-5'-yl sialylethylphosphonate (4) was the most potent inhibitor against rat recombinant alpha-2,3- and alpha-2,6-ST (IC(50) = 0.047, 0.34 mM).

Animals↗
PubMed2005

Synthesis and evaluation of 5-thio-L-fucose-containing oligosaccharide.

5-Thio-L-fucose-containing trisaccharide H-type II was synthesized. The 3',4'-O-isopropylidene-2-azido-2-deoxylactoside derivative, which was prepared from lactose by azidonitration of lactal, was used as a starting material. By regio- and stereoselective 5-thio-L-fucosylation of the 6,6'-dibenzoate 5 with 5-thiofucosyl trichloroacetimidate 6 and subsequent deprotection gave the 5-thio-L-fucose-containing H-type II 1. Conformational analysis of the 5-thio-L-fucose-containing H-type II and the native H-type II was carried out through NOESY experiments. The observed NOE values between N-acetylglucosamine and galactose, and galactose and fucose were same for these two trisaccharides. However, NOE values between fucose and N-acetylglucosamine were significantly different. Binding of the 5-thio-L-fucose-containing H-type II to lectins and antibodies were in some case stronger and in some case weaker than those of the native trisaccharide.

Carbohydrate Sequence↗
PubMed2004

A tong-like fluorescence sensor for metal ions: perfect conformational switch of hinge sugar by pyrene stacking.

Carbohydrates are among the potential materials for molecular devices, since they are abundant natural resources. However, their rigidity has restricted their use for movable devices. Hinge sugars, 2,4-diamino-2,4-dideoxy-xylopyranosides, shed light on the use of carbohydrates as movable components, as demonstrated by the motion by which all four equatorial substituents can change to an axial orientation in synchronization with a chelation-driven 4C1-1C4 ring flip. In this study, we synthesized a tong-like metal ion sensor, 1,3-di-O-pyrenylmethylated hinge sugar (1), and its model compound, methyl 2,4-di-O-pyrenecarbonyl-xylopyranoside (2), to extend the abilities of hinge sugars as molecular components. From observations of the solvent-dependent conformational and fluorescent behavior of 2, we found that the pyrene stacking assists the 1C4 formation of xylopyranoside by 1.7 kcal mol(-1). We also found that compound 1 produced excimer fluorescence by chelation to Pt2+, Zn2+, Cd2+, Mg2+ or Mn2+, and unexpectedly by addition of acids. 1H NMR measurements ascribed this behavior to the 4C1-1C4 ring flip of hinge sugar in response to chelation or protonation at N2, and revealed rapid and perfect 1C4 formation in the case of Zn2+. These findings will extend the scope of hinge sugars as movable components.

Biosensing Techniques↗
PubMed2004

Synthesis of 2-[(2-pyridyl)amino]ethyl beta-D-lactosaminide and evaluation of its acceptor ability for sialyltransferase: a comparison with 4-methylumbelliferyl and dansyl beta-D-lactosaminide.

We reported the synthesis of beta-D-lactosaminide with a 2-aminopyridyl group that is linked to a glycosyl tether at the reducing end. This fluorescent disaccharide acts as an acceptor for both alpha-(2-->6)- and alpha-(2-->3)-sialyltransferases. In addition, the acceptor ability of this disaccharide was evaluated and compared with that of beta-D-lactosaminide having a dansyl or a 4-methylumbelliferyl group.

Animals↗
PubMed2004

Hinge sugar as a movable component of an excimer fluorescence sensor.

[reaction: see text] The ring flip of a carbohydrate is employed for the tongs-like movable component of a metal ion sensor. A pair of separated pyrene groups attached to the carbohydrate component are placed side by side when it recognizes metal ions, affording excimer fluorescence. This novel molecular sensor is selective for Zn(2+) and Cd(2+).

Biosensing Techniques↗
PubMed2004

Diagnostic applicability of dipeptidyl aminopeptidase IV activity in cytological samples for differentiating follicular thyroid carcinoma from follicular adenoma.

HYPOTHESIS: Dipeptidyl aminopeptidase IV (DPP IV) activity in cytological samples from a follicular thyroid tumor is the most sensitive and specific indicator for the detection of follicular carcinoma of the thyroid gland. Dipeptidyl aminopeptidase IV activity is independent of cytological characteristics and superior to other clinical findings. DESIGN AND PATIENT SELECTION: Among the patients surgically treated for follicular thyroid tumors, we recruited approximately equal numbers of those with true-positive (n = 19), true-negative (n = 26), false-negative (n = 16), and false-positive (n = 18) cytological characteristics. MAIN OUTCOME MEASURES: We examined DPP IV activity using cytological specimens obtained from 35 patients with follicular thyroid carcinomas and 44 patients with follicular adenomas. Tumor size, patient age, serum thyroglobulin level, and ultrasonographic findings were also analyzed. RESULTS: The positive rate of DPP IV activity was 97% in 35 patients with follicular thyroid carcinomas and 5% in 44 patients with follicular adenomas, resulting in a sensitivity of 97%, a specificity of 95%, and an overall accuracy of 96%. This discriminating ability of DPP IV activity was far higher than that of tumor size, patient age, serum thyroglobulin level, or ultrasonographic findings. CONCLUSIONS: Positive DPP IV activity in cytological samples is the best discriminatory marker between follicular thyroid carcinoma and follicular adenoma. Its application could alter the clinical management of patients with follicular thyroid tumors.

Adenocarcinoma, Follicular↗
PubMed2004

Immunostaining of galectin-3 and CD44v6 using fine-needle aspiration for distinguishing follicular carcinoma from adenoma.

To evaluate the clinical applicability of galectin-3 and CD44 variant 6 (CD44v6) immunostaining in fine-needle aspiration cytology (FNAC) of thyroid follicular tumors, 79 cytological specimens (35 follicular carcinomas and 44 follicular adenomas) were studied. The positive rates of galectin-3 and CD44v6 were 89 and 74% in follicular carcinoma, respectively, and 25 and 30% in follicular adenoma, respectively. There were no significant correlations between the expression of galectin-3 or CD44v6 in follicular carcinoma and characteristics such as capsular invasion, vascular invasion, metastasis, or tumor size. Positive staining of either galectin-3 or CD44v6 resulted in a diagnostic sensitivity of 97% and a specificity of 52% for follicular carcinoma among follicular tumors. Immunostaining of galectin-3 or CD44v6 using cytological specimens can provide independent information on conventional morphological findings of cytology to distinguish follicular carcinoma from adenoma.

Adenoma↗
PubMed2003

Synthesis of GDP-5-thiosugars and their use as glycosyl donor substrates for glycosyltransferases.

Two thiopyranoside analogues of GDP-sugars, GDP-5-thio-d-mannose (14) and GDP-5-thio-l-fucose (15), were synthesized. The syntheses included the phosphorylations of tetra-O-acetyl-5-thio-d-mannosyl bromide (4) and tri-O-benzoyl-l-fucosyl bromide (6) with silver dibenzyl phosphate, deprotection of the phosphate groups, and condensation of the deprotected phosphates with GMP-imidazolidate (13) in the presence of MgCl(2). These GDP-sugar analogues were found to be donor substrates for alpha(1,2)mannosyltransferase and alpha(1,3)fucosyltransferase, affording a 5-thiomannose-containing disaccharide (18) and a 5-thiofucose-containing trisaccharide (21), respectively. The conformation of the disaccharide analogue 18 was similar to that of its native counterpart by ROESY. These findings for GDP-5-thiosugars together with previous demonstrations of enzymatic transfer from UDP-5-thiosugars will allow the production of panels of oligosaccharide analogues with hydrolase-resistant properties.

Carbohydrate Sequence↗
PubMed2003

Quick aspiration cytology for thyroid nodules by modified Ultrafast Papanicolaou staining.

Quick cytologic diagnosis by Ultrafast Papanicolaou stain (Ultrafast stain) is useful in various neoplastic diseases; however, it has a significant drawback in that the ground-glass appearance of nuclei is a preparation artifact in some specimens from thyroid aspirations. To eliminate this artifact, the nucleus was stained with Gill-5 Hematoxylin (modified Ultrafast stain) rather than with Richard-Allan Hematoxylin 2 in Ultrafast stain. The applicability of this modified Ultrafast stain for quick diagnosis of thyroid diseases was investigated. Two specimens from each of 251 thyroid aspirations (122 malignant and 131 benign) were prepared using the modified Ultrafast stain and the standard Papanicolaou stain. The sensitivities of cytologic diagnosis in specimens stained by the standard Papanicolaou method and the modified Ultrafast method were 95.0% and 93.3%, respectively, and the specificities were 99.2% and 97.7%, respectively. The modified Ultrafast stain is a reliable procedure for quick diagnosis in thyroid aspiration cytology.

Artifacts↗