A modified repulsive bridge correction to accurate evaluation of solvation free energy in integral equation theory for molecular liquids

Integral equation theory for molecular liquids is one of the powerful frameworks to evaluate solvation free energy (SFE). Different from molecular simulation methods, the theory computes SFE in an analytical manner. In particular, the correction method proposed by Kovalenko and Hirata [Chem. Phys. Lett.290, 237 (Year: 1998);Kovalenko and Hirata J. Chem. Phys.113, 2793 (Year: 2000)]10.1063/1.1305885 is quite efficient in the accurate evaluation of SFE. However, the application has been limited to aqueous solution systems. In the present study, an improved method is proposed that is applicable to a wide range of solution systems. The SFE of a variety of solute molecules in chloroform and benzene solvents is evaluated. A key is the adequate treatment of excluded volume in SFE calculation. By utilizing the information of chemical bonds in the solvent molecule, the accurate computation of SFE is achieved

Inhibition of epidermal growth factor-induced cell transformation and Akt activation by caffeine

金沢大学医学部附属病院薬剤部We found that caffeine significantly inhibited epidermal growth factor (EGF)- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation in the JB6 mouse epidermal cell line. The tumor promoter-induced cell transformation was also blocked by treatment with an adenosine A1 receptor antagonist, 8-phenyltheophylline (8-PTH). Caffeine slightly attenuated activation of EGF-induced activator protein 1 (AP-1) activation, which play important roles in cell transformation, but only at the highest concentration examined (1 mM). Interestingly, pretreatment with caffeine suppressed EGF-induced phosphorylation and activation of Akt and ribosomal p70 S6 protein kinase (p70 S6K), a target of Akt, without inhibiting phosphatidylinositol 3-kinase (PI3K) activation. The inhibition of Akt activation of caffeine was not a result of its adenosine receptor antagonism. Because Akt plays a key role in signal transduction pathways leading to cell proliferation and apoptosis, our results provide novel insight into possible mechanisms of the chemotherapeutic effect of caffeine. © 2005 Wiley-Liss, Inc

Structure-activity relationship of flavonoids for inhibition of epidermal growth factor-induced transformation of JB6 CI 41 cells

金沢大学医学部附属病院薬剤部We found that quercetin, myricetin, quercetagetin, fisetin, (-)-epigallocatechin gallate (EGCG), and theaflavins, among 24 flavonoids examined, markedly inhibited epidermal growth factor (EGF)-induced cell transformation of mouse epidermal JB6 Cl 41 cells. The six flavonoids suppressed the EGF-induced activation of activator protein 1 (AP-1). In addition, myricetin, quercetagetin, EGCG, and theaflavins directly inhibited EGF-induced phosphatidylinositol 3-kinase (PI3K) activation. The important structural features of flavonoids for cell transformation-inhibitory activity are 3′- and 4′-OH on the B-ring, 3-OH on the C-ring, C2=C3 double bond in the C-ring, and the phenylchromone (C6-C5-C6) skeleton in the flavonols, and the galloyl group in EGCG and theaflavins. Our results provide new insight into possible mechanisms of the anti-carcinogenic effects of flavonoids, and could help to provide a basis for the design of novel cancer chemopreventive agents. © 2007 Wiley-Liss, Inc

Identification of a new interaction mode between the Src homology 2 domain of C-terminal Src kinase (Csk) and Csk-binding protein/phosphoprotein associated with glycosphingolipid microdomains

This research was originally published in Journal of Biological Chemistry. Hiroaki Tanaka, Ken-ichi Akagi, Chitose Oneyama, Masakazu Tanaka, Yuichi Sasaki, Takashi Kanou, Young-Ho Lee, Daisuke Yokogawa, Marc-Werner Dobenecker, Atsushi Nakagawa, Masato Okada and Takahisa Ikegami. Identification of a new interaction mode between the Src homology 2 domain of C-terminal Src kinase (Csk) and Csk-binding protein/phosphoprotein associated with glycosphingolipid microdomains. Journal of Biological Chemistry. 2013; 288, 15240-15254. © the American Society for Biochemistry and Molecular Biology

ヨウバイ コウゾウ ト デンシ コウゾウ ニ チャクモクシタ ヨウバイワ リロン ノ カイハツ

京都大学0048新制・課程博士博士(工学)甲第14167号工博第3001号新制||工||1445(附属図書館)26477UT51-2008-N484京都大学大学院工学研究科分子工学専攻(主査)教授 榊 茂好, 教授 田中 一義, 教授 田中 庸裕学位規則第4条第1項該当Doctor of EngineeringKyoto UniversityDFA

The development of a revised version of multi-center molecular Ornstein–Zernike equation

Ornstein–Zernike (OZ)-type theory is a powerful tool to obtain 3-dimensional solvent distribution around solute molecule. Recently, we proposed multi-center molecular OZ method, which is suitable for parallel computing of 3D solvation structure. The distribution function in this method consists of two components, namely reference and residue parts. Several types of the function were examined as the reference part to investigate the numerical robustness of the method. As the benchmark, the method is applied to water, benzene in aqueous solution and single-walled carbon nanotube in chloroform solution. The results indicate that fully-parallelization is achieved by utilizing the newly proposed reference functions

Analytical energy gradient for reference interaction site model self-consistent field explicitly including spatial electron density distribution

Analytical energy gradient formula was derived for reference interaction site model self-consistent field explicitly including spatial electron density distribution (RISM-SCF-SEDD). RISM-SCF-SEDD is a combination method of ab initio electronic structure theory and statistical mechanics for molecular liquids [ D. Yokogawa et al., J. Chem. Phys. 126, 244504 (2007) ]. As shown previously, RISM-SCF-SEDD is numerically stable and has expanded the applicability of the solvation theory. The energy gradient is an indispensable tool to compute molecular geometry and its implementation further extends the capability of RISM-SCF-SEDD. The present method was applied to chemical systems in aqueous solution; hydration structure and geometry of phosphate anion PO43− and tautomerization between 2-pyridone and 2-hydroxypyridine. Compared to available experimental data, the present method correctly reproduced the geometries and relative energies of solvated molecules with microscopic solvent distribution. It is clearly shown that highly sophisticated quantum chemical calculation such as coupled cluster with single and double and perturbative triple excitations coupled with solvation effect is a powerful tool to accurately evaluate molecular properties

Theoretical study on aquation reaction of cis-platin complex: RISM-SCF-SEDD, a hybrid approach of accurate quantum chemical method and statistical mechanics.

The ligand exchange process of cis-platin in aqueous solution was studied using RISM-SCF-SEDD (reference interaction site model-self-consistent field with spatial electron density distribution) method, a hybrid approach of quantum chemistry and statistical mechanics. The analytical nature of RISM theory enables us to compute accurate reaction free energy in aqueous solution based on CCSD(T), together with the microscopic solvation structure around the complex. We found that the solvation effect is indispensable to promote the dissociation of the chloride anion from the complex