Amino acids and peptides. XIII. Synthetic studies on N-terminal tripeptide amide analogs of fibrin alpha-chain

N-Terminal tripeptide analogs of fibrin alpha-chain were synthesized and their inhibitory effect on fibrinogen/thrombin clotting was examined. A new water-soluble active ester, 3-pyridinium ester, was used for the synthesis. Among the synthetic peptides, H-Gly-Pro-Arg-hexamethyleneimine exhibited the highest inhibitory effect on fibrinogen-thrombin clotting.     

Stochastic optimization of forward recursive functions

This note solves a finite-horizon stochastic optimization problem with forward recursive criterion through dynamic programming. The forward recursive criterion is wide; it includes additive (discounted), multiplicative (discounted risk-sensitive), minimum and terminal criteria. The basic idea is to apply invariant imbedding method for the stochastic optimization. The method incorporates recursive accumulation process into dynamics by expanding the original state space.     

Synthesis of copolymers containing a spiro orthocarbonate moiety and evaluation of the volume change during their cationic crosslinking

Spiro orthocarbonate (SOC) monomers having either an exomethylene group {3,3‐dimethyl‐9‐methylene‐1,5,7,11‐tetraoxaspiro[5.5]undecane (ExoSOC)} or an allyl group {9‐allyl‐3,3‐dimethyl‐1,5,7,11‐tetraoxaspiro[5.5]undecane (AllylSOC)} were radically copolymerized with vinyl monomers at several feed ratios to obtain the corresponding copolymers having SOC moieties in the side chain. The obtained copolymers were crosslinked via the double ring‐opening polymerization of the SOC moieties by a treatment with boron trifluoride etherate. The volume changes during the crosslinking of the copolymers were evaluated by density measurements with a gas pycnometer. As the SOC moiety composition increased, the volume shrinkage during the crosslinking was suppressed, and that finally changed into volume expansion. The volume changes during the crosslinking of the copolymers from AllylSOC were slightly larger than those of the copolymers from ExoSOC. The higher volume expansions in the crosslinking of AllylSOC‐based copolymers were ascribable to the lower steric hindrance around the SOC moieties. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 7040–7053, 2006     

Vascular dilatory action of the Chinese crude drug. II. Effects of scoparone on calcium mobilization

Further experiments were conducted to examine the effect of scoparone (6,7-dimethoxycoumarin), a coumarin derivative found in the Chinese crude drug "Capillaris Flos," on calcium mobilization. Scoparone does not affect Ca2+ influx through the voltage-dependent channel due to membrane depolarization. Its inhibitory action may be dependent not only on the inhibition of Ca2+ release from sarcoplasmic reticulum but also on the inhibition of extracellular Ca2+ influx through the receptor-operated channel.     

Synthesis and antiallergy activity of [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives. II. 6-Alkyl- and 6-cycloalkylalkyl derivatives.

A series of 6-alkyl- or 6-(cycloalkylalkyl)-[1,3,4]thiadiazolo[3,2- a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-ones 1b--o was synthesized from the corresponding 1,3,4-thiadiazol-5-amines 3b--o and the antiallergic activities of the products were evaluated. Among the compounds 6-(2-cyclohexylethyl)- [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one 1h, whose X-ray crystallographic stereostructure is shown, was found to be a promising new antiallergic agent, which has low toxicity and dual activity as a leukotriene D4 receptor antagonist and as an orally active mast cell stabilizer.     

Synthesis,surface accumulation,and micellar properties of amphiphilic block copolymers

Amphiphilic block copolymers, i.e., poly(methyl methacrylate)-b-poly(2-dimethylethylammoniumethyl methacrylate), were synthesized by the reaction between two prepolymers. Carboxyl-terminated poly(methyl methacrylate) and hydroxyl-terminated poly(2-dimethylaminoethyl methacrylate) were prepared by radical polymerization of the corresponding monomers in the presence of thioglycolic acid and 2-mercaptoethanol as a chain transfer agent, respectively. Two condensation methods, i.e., DCC and the acid chloride method, were used for the reactions of these prepolymers. The subsequent quarternization produced the amphiphilic block copolymers. Surface property of poly(methyl methacrylate) films containing this amphiphilic block copolymer was examined by measuring contact angles for water. The addition of only 0.5 wt% of the block copolymer was sufficient to make poly(methyl methacrylate) surfaces hydrophilic. The block copolymer formed a polymeric micelle in acetone–water mixed solvent.     

Visualization of complexes of Hoechst 33258 and DNA duplexes in solution by atomic force microscopy

Tertiary structure changes in DNA duplexes, induced by Hoechst 33258 binding, have been examined by the use of atomic force microscopy. Besides minor groove binding, which is an established mode of binding for this drug, Hoechst 33258 has now been found to show another binding mode, which causes an unwinding of the duplex. When the drug concentration is as high as 0.5 microg/ml, the Hoechst 33258 molecule seems to function as a clamp for two DNA chains and forms a condensate. The condensate was found to have a toroidal shape. By surveying more than 100 microscopic images of such condensates formed in I microg/ml drug solution, a mechanism of toroidal condensate formation has been proposed.     

High-performance liquid chromatographic procedure for the simultaneous determination of norfloxacin, fenbufen and felbinac in rat plasma

A high-performance liquid chromatographic method for the simultaneous determination of norfloxacin, fenbufen and felbinac extracted from 50 microliters of rat plasma is described. Chromatography was performed on a reversed-phase column with ultraviolet detection. By the present method, quantitative and reproducible determinations were possible for norfloxacin, fenbufen and felbinac over the concentration ranges of 0.2-20, 0.2-120 and 0.4-40 micrograms/ml, respectively. The recoveries of norfloxacin, fenbufen and felbinac added to plasma were nearly 100% with a coefficient of variation of less than 8.0%. This method was found to be applicable to pharmacokinetic studies of each drug after the concomitant administration of norfloxacin and fenbufen.