Yasuyuki Kitagawa

Vibrational spectra and structures of zinc carboxylates I. Zinc acetate dihydrate

Abstract The crystal structure of zinc acetate dihydrate was re-refined by X-ray diffraction analysis of the single crystal. The monoclinic cell dimensions were revised as a=14.394 (3), b=5.330 (2), c=10.962 (3) A and β=99.8 (2)° with Z=4. The bond distances and bond angles were also refined. Based on the structure, a normal mode analysis was made and the valence force constants were determined. Precise spectral assignments were made. Based on the assignments and the structure, the relation between the coordination forms and the vibrational frequencies of the carboxylate antisymmetric stretch and the symmetric stretch were discussed. In order to identify the coordination form of the carboxylate group from the vibrational frequencies, we propose the importance of other carboxylate modes other than the stretches.

Zinc(II) acetate dihydrate

The Zn atom in bis(acetato-O,O′)diaquazinc(II), [Zn(CH3COO)2(H2O)2], adopts a distorted octahedral structure coordinated by two water O atoms and four acetate O atoms.

Primary structure and characterization of a non hemorrhagic metalloproteinase with fibrinolytic activity, from the snake venom of Protobothrops tokarensis (Tokara-habu).

A low molecular weight metalloproteinase, named PT-H₂ protease, with fibrinolytic activity, was purified from the venom of Protobothrops tokarensis (Tokara-habu) by gel-filtration using Sephadex G-100, and ion-exchange chromatographies using CM-Sepharose Fast Flow and Mono S HR 5/5. By this procedure, about 85 mg of purified protein were obtained from 1.0 g of P. tokarensis venom. The purified protein showed a single protein band with a molecular weight of about 22.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. The pI of purified protein showed a single band of 6.8. This proteinase showed a strong fibrinolytic activity. Further, this proteinase showed fibrinogenase activity and proteolytic activity against synthetic substrates for matrix metalloproteinase, ADAM-17, and TACE (tumor necrosis factor converting enzyme). These proteolytic activities were inhibited by metalloproteinase inhibitors such as EDTA. PT-H₂ protease consisted of 201 amino acid residues and had a calculated molecular weight of 22,994.7 Da. This protein showed conservation of the Zn²⁺-binding HEXXHXXGXXHD sequence. PT-H₂ protease showed high homology from 51.7 to 99.5% with amino acid sequences of other snake venom metalloproteinases.

Tuning efficiency of the 4-exo-trig cyclization by the electronic effect: ring closure of 3,3-difluoro-4-pentenyl carbon radicals and synthesis of a gem-difluorocyclobutane nucleoside

4-exo-trig Cyclization reaction of a 4-pentenyl carbon radical containing the gem-difluoromethylene moiety adjacent to a radical accepting α,β-unsaturated ester was found to proceed efficiently to furnish a novel gem-difluorocyclobutane derivative. The cyclized product could be transformed into a gem-difluoromethylene analogue of oxetanocin T.

Novel concept of enzyme selective nicotinamide adenine dinucleotide (NAD)-modified inhibitors based on enzyme taxonomy from the diphosphate conformation of NAD

The dihedral angle θ of the diphosphate part of NAD(P) were investigated to distinguish the differences in the binding-conformation of NAD(P) to enzymes and to create an enzyme taxonomy. Furthermore, new inhibitors with fixed dihedral angles showed that enzymes could recognize the differences in the dihedral angle θ. We suggest the taxonomy and the dihedral angle θ are important values for chemists to consider when designing inhibitors and drugs that target enzymes.

Efficient Synthesis of a Water-Soluble Glucoamide Inhibitor Against Human Aldose Reductase by Click Chemistry

While D-glucose is the natural substrate of aldose reductase (AR) in the polyol pathway, the K m value of D-glucose against AR is large. A glucoamide 1 was designed as a tool to investigate whether AR has a strong affinity for the open form of D-glucose. Glucoamide 1 was synthesized in high yield by modification of the reaction condition for click chemistry. It was found that our modified condition was applicable for highly polar alkynes and gave coupling products in excellent yield (90% to 100%). Although weak inhibitory activity against AR was observed, kinetic studies showed that AR does not accept glucoamide 1 in its active site.