Akira Gonda

Pseudostellarins D-F, new tyrosinase inhibitory cyclic peptides from Pseudostellaria heterophylla

Abstract New potent tyrosinase inhibitory cyclic peptides, pseudostellarins D - F, have been isolated from the roots of Pseudostellaria heterophylla and the structures were elucidated by extensive 2D NMR methods, chemical and enzymatic degradation and ESI tandem MS spectroscopic analysis.

Cycloleonuripeptide D, a new proline-rich cyclic decapeptide from Leonurus heterophyllus

Abstract A new proline-rich cyclic decapeptide, cycloleonuripeptide D (1), cyclo (-Ser-Pro-Pro-Tyr-Phe-Gln-Thr-Pro-Ile-), was isolated from the fruits of Leonurus heterophyllus and the structure was elucidated by extensive 2D NMR, chemical and enzymatic degradation studies, and tandem MS method. The solid state conformation of cycloleonuripeptide D was clarified by X-ray diffraction study. The cyclic decapeptide backbone of 1 contained two β-turns, one type I β-turn at Pro-Ile and one type III β-turn at Pro-Tyr. A transannular 4 → 1 backbone hydrogen bond between Ser-NH and Thr-CO, and a 5 → 1 hydrogen bond between Phe-NH and Pro-Co encompassing Pro-Pro-Tyr, in which the peptide linkage between the two proline residues was shown to be in the cis conformation, were observed.

3D QSAR analysis of taxoids from Taxus cuspidata var. nana by comparative molecular field approach

Abstract A series of taxoids, isolated from the stems of Taxus cuspidata var. nana , showing a cell growth inhibitory activity, were investigated for their 3D QSAR by using the comparative molecular field (CoMFA) analysis. The results indicated a strong correlation between the P388 cell growth inhibitory activity of these taxoids and the steric and electrostatic factors which modulate their biological activity, and accounted for the potent activities of the taxoids with the N-acylphenylisoserine derivatives at C-13 and the weak activities of those without this kind of ester group. It was also suggested that the substituent at C-2 is not a requisite for the biological activity: smaller substituent seemed to favor the biological activity.

Cycloleonuripeptides A, B and C, three new proline-rich cyclic nonapeptides from Leonurus heterophyllus

Abstract Three new proline-rich cyclic nonapeptides, cycloleonuripeptides A: cyclo (-Gly-Pro-Pro-Pro-Tyr-Pro-Pro-Met-Ile-), B: cyclo (-Gly-Pro-Pro-Pro-Tyr-Pro-Pro-Met(O)-Ile-), and C: cyclo (-Gly-Pro-Pro-Pro-Tyr-Pro-Pro-Met(O)-Ile-), have been isolated from the fruits of Leonurus heterophyllus and their structures were elucidated by extensive 2D NMR methods, chemical degradation and transformation. Cycloleonuripeptides B and C, both of which are epimer, showed cell growth inhibitory activity.

Solution state conformation of an immunosuppressive cyclic dodecapeptide, cycloleonurinin

Abstract The cyclic dodecapeptide, cycloleonurinin, cyclo(-Gly-Pro-Thr-Gln-Tyr-Pro-Pro-Tyr-Tyr-Thr-Pro-Ala-), isolated from the fruits of Leonurus heterophyllus, showed potent immunosuppressive effect on human peripheral blood lymphocytes. The solution state conformation of cycloleonurinin was examined by high field NMR methods, distance geometry calculation and restrained energy minimization from NMR data. Calculation using 277 different initial structures led to a uniquely determined backbone conformation with a root mean square deviation value of 0.80 A. The backbone structure of cycloleonurinin consists of two β-turns, a β VI turn at Pro6-Pro7, and a β I turn at Pro11-Ala12. In addition to two transannular 4 → 1 backbone hydrogen bonds, which constructed two β-turns, two intramolecular hydrogen bonds between Tyr9-NH and Pro7-CO, and between Thr10-NH and Tyr8-CO, constructing γ-turns, and those between Thr3-NH and Tyr8-CO, and between Ala12-NH and Thr10-OH, were observed.

A taxoid from Taxus cuspidata var. nana

A new taxoid, named taxuspinanane C, has been isolated from the stems of Taxus cuspidata Sieb. et. Zucc. var. nana Rehder. and the structure was elucidated by extensive 2D NMR methods.

CRYSTAL AND SOLUTION STATE CONFORMATIONS OF TWO TAXOIDS, TAXININE AND TAXININE B

Abstract Crystal and solution state conformations of two taxoids, taxinine and taxinine B, inhibiting the drug transport by P-glycoprotein in multidrug-resistant cells, were analyzed by X-ray crystallographic analysis and ROE experiments. This study demonstrated that in solid state, both taxinine and taxinine B took similar cage conformation in which A-ring and the cinnamoyl side chain at C-ring were specially very close to each other. These conformations were also observed in their solution conformations deduced by ROE correlations in CDCl3, Monte Carlo simulation using MM2∗ force field, and semiempirical molecular orbital calculation using PM3 method.