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Biomedical subjects

Yukio Hitotsuyanagi

Publications and source records attributed to Yukio Hitotsuyanagi.

8 recordsLinked to original sources
PubMed2004

RA-VII, a cyclic depsipeptide, changes the conformational structure of actin to cause G2 arrest by the inhibition of cytokinesis.

In L1210 cells, RA-VII (0.1-100 nM) caused the concentration-dependent inhibition of the proliferation and G2 arrest. Treatment of PC12 cells with 10 nM RA-VII changed cell shape round with binucleation, suggesting the inhibition of cytokinesis. The fluorescence intensity of FITC-phalloidin bound to F-actin was enhanced by RA-VII. In surface plasmon resonance experiments, the signal of F-actin was modified by RA-VII in close agreement with a concentration of FITC-phalloidin binding to F-actin. These results suggest that RA-VII causes the conformational change of F-actin and the stabilization of actin filaments to induce G2 arrest.

Actins↗
PubMed2004

Semisynthesis of an analogue of antitumor bicyclic hexapeptide RA-VII by fixing the Ala-2/Tyr-3 bond to Cis by incorporating a triazole cis-amide bond surrogate.

We prepared an analogue of an antitumor bicyclic hexapeptide RA-VII whose amide configuration between residues 2 and 3 was fixed to cis by incorporating a triazole cis-amide bond surrogate. This analogue was shown, by NMR studies, to take almost the same conformation as that of the minor conformer of RA-VII. It showed no cytotoxic activity.

Alanine↗
PubMed2004

Synthesis of [Gly-1]RA-VII, [Gly-2]RA-VII, and [Gly-4]RA-VII. Glycine-containing analogues of RA-VII, an antitumor bicyclic hexapeptide from Rubia plants.

Three analogues of RA-VII (1), an antitumor bicyclic hexapeptide from Rubia plants, were synthesized. Three analogues, [Gly-1]RA-VII (4), [Gly-2]RA-VII (5), and [Gly-4]RA-VII (6), in which one of the three alanine residues in 1 was replaced by a glycine residue, were prepared by linking of the cycloisodityrosine unit, obtained by degradation of 1, to three different glycine-containing tetrapeptides followed by macrocyclization. Of these three analogues, analogue 4 showed the highest cytotoxic activity. The NMR study revealed that in solution the conformer structures and their ratios of analogue 4 were very similar to those of natural peptide 1, suggesting that the methyl groups at Ala-2 and Ala-4 should be essential for producing the bioactive conformation, whereas that at D-Ala-1 is not essential.

Animals↗
PubMed2004

New quassinoids, javanicolides C and D and javanicosides B--F, from seeds of Brucea javanica.

Two new quassinoids, javanicolides C and D, and five new quassinoid glucosides, javanicosides B-F, were isolated from the seeds of Brucea javanica, along with eight known quassinoids, i.e., yadanziolides A, C, D, and S, bruceins D and E, brusatol, and the aglycone of yadanzioside D, and 19 known quassinoid glucosides, i.e., yadanziosides A-G, I, and K-P, bruceosides A-C and E, and bruceantinoside A. Their structures were elucidated by analysis of spectroscopic data and chemical evidence.

Brucea↗
PubMed2003

Synthesis of [L-Ala-1]RA-VII, [D-Ala-2]RA-VII, and [D-Ala-4]RA-VII by epimerization of RA-VII, an antitumor bicyclic hexapeptide from Rubia plants, through oxazoles.

Three epimers of a natural cyclic hexapeptide RA-VII were prepared via formation of oxazoles from thioamides or thioimidates of RA-VII followed by hydrolysis. They are the epimers at l-Ala-1, d-Ala-2, and d-Ala-4, respectively. The one having l-Ala-1 adopted trans-cis-trans-trans-trans-trans (t-c-t-t-t-t) amide configurations in the crystal, a type-VI beta-turn for residues 1-4 stabilized by one intramolecular hydrogen bond between Ala-4 NH and l-Ala-1 C = O, and in CDCl(3) existed as a mixture of six conformers, of which the major conformer was very similar to that in the crystal, but quite different from that of RA-VII in solution. The second epimer, having d-Ala-2 had in the crystalline state t-t-t-t-c-t amide configurations, a gamma-turn at Tyr-3 stabilized by two intramolecular hydrogen bonds between d-Ala-2 NH and Ala-4 C = O and between Ala-4 NH and d-Ala-2 C = O, and existed in CDCl(3) as a single conformer, the structure of which was very similar to its crystal structure, and to the crystal structure of peptide 25 except for the backbone and the side chains at residues 1 and 2. The third epimer, having d-Ala-4 had t-c-t-t-c-t amide configurations in the crystal, a type-VI beta-turn for residues 1-4 as observed in the first epimer, and in CDCl(3) existed in three conformers, of which the major one was similar to that in the crystal but different from that of RA-VII in solution. The three epimers showed very weak cytotoxicity on P-388 leukemia cells, which may be because of their conformational differences from the active conformation of RA-VII.

Alanine↗
PubMed2002

A cis amide bond surrogate incorporating 1,2,4-triazole.

A novel cis amide bond surrogate incorporating 1,2,4-triazole was designed and synthesized by the reaction of a thionotripeptide, formic hydrazide, and mercury(II) acetate. This method of surrogate formation was also applicable to a cyclic thionopeptide.

Amides↗
PubMed2002

Quassinoids from Eurycoma longifolia.

Three quassinoids, eurycolactone D (1), eurycolactone E (2) and eurycolactone F (3) were isolated from the roots of Eurycoma longifolia Jack. The structures of 1-3 were elucidated by spectroscopic methods, and that of 3 was further confirmed by X-ray crystallography. The known quassinoids, laurycolactone B (4) and eurycomalactone (5) were also identified.

Crystallography, X-Ray↗