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Biomedical subjects

T Morikawa

Publications and source records attributed to T Morikawa.

At least 253 records · Page 14Linked to original sources
PubMed1982

Partial purification of a procollagen C-proteinase. Inhibition by synthetic peptides and sequential cleavage of type I procollagen.

A procollagen C-proteinase which cleaves the C-propeptides from type I procollagen was purified about 125-fold from membranous bones of chick embryos. As estimated by gel filtration, the enzyme was about 80 000 daltons. When a reaction with modified procollagen was carried out, the enzyme preferentially cleaved the C-propeptides from the pro alpha chains in the order pro alpha 1, pro alpha 1, and then pro alpha 2. The enzyme was inhibited by several metal chelators and high concentrations of dithiothreitol. It was also inhibited by 5% fetal calf serum. A series of inhibitors of serine proteinases and sulfhydryl-containing proteinases were not inhibitory. Four oligopeptides were synthesized with amino acid sequences similar to the amino acid sequences around the sites at which the C-propeptides are cleaved during the conversion of procollagen top collagen in vivo. The peptide Tyr-Tyr-Arg-Ala-Asp-Asp-Ala inhibited the enzyme 35--60% in concentrations of 6--12 mM. Shorter peptides containing the Ala-Asp bond cleaved by the enzyme were less effective. The partially purified enzyme was also found to cleave the C-propeptides from type II and type III procollagens.

Animals↗
PubMed1982

A new class of nitrosoureas. 4. Synthesis and antitumor activity of disaccharide derivatives of 3,3-disubstituted 1-(2-chloroethyl)-1-nitrosoureas.

A series of 33 N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of N-substituted glycosylamines has been prepared and tested for antitumor activities. The compounds were obtained by reaction of glycosylamines with isocyanate, followed by nitrosation with N2O4. Structure-activity relationships of these trisubstituted nitrosoureas were investigated by varying the N-substituents and disaccharide groups and by comparing them with the corresponding disubstituted analogues. A large number of the nitrosoureas bearing a maltosyl group exhibited strong antitumor activities against leukemia L1210 and Ehrlich ascites carcinoma, and 60-day survivors against leukemia L1210 were found at the optimal dose for these derivatives. In contrast, the lactosyl and the melibiosyl derivatives were almost inactive. The most interesting compound in this series, the 3-isobutyl-3-maltosyl derivative (37), was tested against leukemia L1210 by single and multiple treatment. Its therapeutic ratio (96.3) obtained by multiple treatment is 3 times larger than that (31.5) obtained by single treatment, suggesting a possible clinical utility of 37 by multiple treatment. The favorable effect of a maltosyl moiety in this class of compounds is discussed.

Animals↗
PubMed1981

Preferential hydration of bovine serum albumin in polyhydric alcohol-water mixtures.

The preferential solvent interaction with bovine serum albumin in aqueous solution of polyhydric alcohols (ethylene glycol, glycerol, xylitol, sorbitol, mannitol, and inositol) was investigated by a densimetric method with the application of multicomponent theory. This proteins was preferentially hydrated in all solvent systems examined: the extent depended on the number and the steric configuration of the hydroxyl groups of alcohols. The absolute interactions of these alcohols with the protein were estimated by assuming that the amount of hydration of protein at every solvent composition used is identical with that in pure water. The preferential hydration of the protein in 30% aqueous solutions of glycerol and sorbitol was found to decrease as the temperature was increased, indicating that the increase in chemical potential of protein on transferring it from water to both aqueous solvents is generated by a large positive enthalpy change, sufficient to compensate for the positive entropy change in the transfer process. On the basis of these results, and mechanism of stabilization of protein structure by these alcohols was discussed from the viewpoint of the solvation of protein.

Alcohols↗
PubMed1981

Thermodynamics of polyol-induced thermal stabilization of chymotrypsinogen.

In order to clarify the mechanism of polyol-induced stabilization of protein, the thermodynamic parameters (delta G degree, delta H degree, and delta S degree) of thermal denaturation of chymotrypsinogen have been measured in aqeous solutions of some polyols (ethylene glycol, erythritol, adonitol, sorbitol, mannitol, and inositol) by a differential spectrophotometric method. On increasing the alcohol concentration and the number of hydroxymethyl groups of the alcohols, delta G degree increased as a result of a large decrease in delta S degree compensating for a decrease in delta H degree. This result means that the stabilization of this protein by polyols is due to the entropy effect, and that the free energy change of transfer of the denatured protein from water to aqueous media containing these alcohols must be larger than that of the native protein. This strongly supports the previous proposal that the driving force of protein stabilization induced by polyols is a solvent medium effect or a solvent ordering effect. The decreases in delta H degree and delta S degree with polyols are expected to be more due to the effects of polyols on peptide-water interactions than to exposed nonpolar groups of denatured protein.

Alcohols↗