An efficient in silico screening method based on the protein-compound affinity matrix and its application to the design of a focused library for cytochrome P450 (CYP) ligands

A new method has been developed to design a focused library based on available active compounds using protein-compound docking simulations. This method was applied to the design of a focused library for cytochrome P450 (CYP) ligands, not only to distinguish CYP ligands from other compounds but also to identify the putative ligands for a particular CYP. Principal component analysis (PCA) was applied to the protein-compound affinity matrix, which was obtained by thorough docking calculations between a large set of protein pockets and chemical compounds. Each compound was depicted as a point in the PCA space. Compounds that were close to the known active compounds were selected as candidate hit compounds. A machine-learning technique optimized the docking scores of the protein-compound affinity matrix to maximize the database enrichment of the known active compounds, providing an optimized focused library.     

Multiattribute utility analysis for policy selection and financing for the preservation of the forest

In this paper, we examine effective policies for financing and activities for the preservation of the forest on Mount Ryuoh in the city of Higashi-Hiroshima by multiattribute utility analysis. In multiattribute utility analysis, we deal with decision making problems with multiple attributes and select the most effective solution among several alternatives by deriving preference of the decision maker. Although in our decision making problem, the decision maker is a representative of a hypothetical nonprofit organization established for the preservation of the forest, the decision maker gives serious consideration to intentions of several groups of people receiving the benefit from the mountain, and then from this viewpoint, our problem can be interpreted as a group decision making problem.     

Solid-phase combinatorial synthesis of aeruginosin derivatives and their biological evaluation

A 24-member combinatorial library based on the structure of aeruginosin 298-A (1a) was synthesized utilizing solid-phase, and their inhibitory activity against trypsin was evaluated. Among the library, we found that D-Hpla-D-Leu-L-Choi-Agma (1h) is 300 times more potent than the parent natural product 1a.     

Radical polymerization of muconic acid and ethyl muconate

Muconic acid (Mu-acid) was found to polymerize to trans-1,4-poly(Mu-acid) with the use of azobisisobutyronitrile (AIBN) as an initiator. Similarly, a muconic acid derivative, ethyl muconate (EMu), was readily polymerized through a trans-1,4 addition mechanism by the use of a radical or anionic catalyst, but did not polymerize when a cationic catalyst such as boron trifluoride etherate was used. Moreover, the copolymerization of Mu-acid and EMu with various comonomers such as styrene, acryronitrile, and 2-vinylpyridine was carried out and Q–e values of Mu-acid and EMu are discussed. These substituted diene monomers always polymerized through trans-1,4 addition with all catalysts and any comonomers.     

Chemical Modification of Chitosan, 17

The Michael reaction of chitosan with acrylic acid was carried out successfully, even in water alone as the reaction medium. As a consequence of its good solubility in water, the reaction product, N‐carboxyethylchitosan, showed excellent biodegradable properties with standard activated sludge.

     

Ring transformation of pyrimidines to pyridines. Synthesis of 4-alkylaminopyridin-2-ones by alkaline hydrolysis of 6-(2-dimethylaminovinyl)uracils

Alkaline hydrolysis of 1,3-disubstituted 6-(2-dimethylaminovinyl)uracils 2 induced a novel ring transformation giving 4-alkylaminopyridin-2-ones 3 via ring-opening and ring-closure processes. The 4-methylamino-3-nitropyridin-2-one ( 3a ) thus obtained was employed for the synthesis of 3-deazahypoxanthine derivative 8. 4-Alkylamino-3-cyanopyridin-2-ones 11 , ricinine analogs, were also prepared by the reaction of 4-chloro-3-cyano-1-methylpyridin-2-one ( 10 ) with amines.     

THE EFFECT OF ALIPHATIC ALCOHOLS ON FLUORESCENCE QUENCHING AND FLUORESCENCE POLARIZATION OF LUMINESCENCE PROBES IN HEXADECYLTRIMETHYLAMMONIUM BROMIDE MICELLES

Abstract— The fluorescence quenching of the indole chromophore by NO⁻₂ and the fluorescence depolarization of several luminescence probes in aqueous solutions containing hexadecyltrimethylammonium bromide (HDTBr) were measured as a function of added C₂–C₄ aliphatic alcohol concentration. The fluorescence decay profiles of pyrene in the micellar solutions were also measured to estimate the aggregation number of the micelles. The addition of n -butyl alcohol significantly reduces the fluorescence quenching rate and the aggregation number and increases the extent of fluorescence depolarization in HDTBr micellar systems. The addition of ethyl alcohol shows a similar but smaller effect.     

Synthesis and Absolute Configuration at C(8) of ‘p‐Menthane‐3,8,9‐triol’ Derived from (–)‐Isopulegol

Two diastereoisomers of the new, potentially insecticidal ‘p‐menthane‐3,8,9‐triol’ (=(2S)‐ and (2R)‐ 2‐[(1R,2R,4R)‐2‐hydroxy‐4‐methylcyclohexyl]propane‐1,2‐diol; (8S)‐ and (8R)‐ 1 ), have been synthesized from (–)‐isopulegol by both conventional dihydroxylation and catalytic Sharpless dihydroxylation (Scheme). The absolute configuration at C(8) of the corresponding orthoformate adduct (8S)‐ 3a was determined by ¹H‐NMR and X‐ray crystallographic analysis (Figure).