Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry最新文献

The mutagenic title compound (5,8-DiMeIQx) was synthesized by two different routes: from 2-methyl-4,6-dinitroaniline; and from 4-chloro-2-methyl-6-nitroaniline. The latter and more convenient route involved 2,1,3-benzoselenadiazole intermediates.

Misincorporation of 2-hydroxyethylated amino acids into hemoglobin during de novo synthesis was studied by injecting mice with radiolabelled N-(2-hydroxyethyl)valine, S-(2-hydroxyethyl)cystine or N tau-(2-hydroxyethyl)histidine. The results showed that S-(2-hydroxyethyl)cysteine and N tau-(2-hydroxyethyl)histidine were misincorporated, whereas N-(2-hydroxyethyl)valine was not. Monitoring of in vivo doses of hydroxyethylating agents by determination of N-(2-hydroxyethyl)valine was free of the disturbing influence of such misincorporation.

The activity of cholesterol 7 alpha-hydroxylase in rat liver microsomes was investigated under conditions favourable for phosphorylation-dephosphorylation. The enzyme activity was similar in the presence or absence of sodium fluoride during preparation. Preincubation with ATP and magnesium did not affect the enzyme activity. Cholesterol 7 alpha-hydroxylase was inhibited by alkaline phosphatase, but this inhibition was similar also after inactivation of the phosphatase. Under similar conditions, rat hepatic hydroxymethylglutaryl CoA reductase activity was clearly modulated in agreement with phosphorylation-dephosphorylation. The absence of such a modulation of cholesterol 7 alpha-hydroxylase argues against involvement of phosphorylation-dephosphorylation in the regulation of this enzyme.

Hydrogen peroxide is catalytically disproportionated by lactoperoxidase in the presence of iodide ions, Km = 55 microM in 100 mM sodium phosphate, pH 7.00, 25 degrees C. Products formed are water and molecular oxygen. The reaction is competitively inhibited by hydrogen sulfite, Ki = 0.24 mM in 100 mM sodium phosphate, pH 7.00, 25 degrees C. The stoichiometry of the reaction is identical with the corresponding catalase reaction but the mechanism differs. A mechanistic model for lactoperoxidase-iodide dismutation of hydrogen peroxide is discussed.

The heptapeptide Tyr-Arg-Glu-Asp-Met-Glu-Tyr-OMe, spanning region 213-219 of Escherichia coli K88 ab protein fimbriae, was synthesized with an overall yield of 37% using dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) preactivation in all condensation reactions. The C-terminal was protected as the methyl ester. The protection scheme of N alpha-tert-butyloxycarbonyl-(Boc) and benzyl-(Bzl) or benzyloxycarbonyl (Z) groups for side chain protection was found to be orthogonal when a mixture of trifluoroacetic acid (TFA), phenol (PhOH) and p-cresol (CrOH) was used for repetitive deprotection. The final deprotection of Boc-Tyr(Bzl)-Arg(Z2)-Glu(Bzl)-Asp(Bzl)-Met-Glu(Bzl+ ++)-Tyr(Bzl)-OMe (17) was accomplished in 80% yield by prolonged treatment with hydrogen fluoride, dimethyl sulfide, p-cresol and p-thiocresol. The BSA-linked synthetic peptide was used in immunisation experiments on rabbits.

Synthesis and bioassay of about 65 analogs of substance P (SP) over five years yielded the antagonist [D-Arg1,D-Trp7,9,Leu11]-SP, which was named Spantide, and which was used by many investigators as a "tool". Spantide served as a reference antagonist for the design of 47 new peptides toward the goal of more potent inhibitors. Designs emphasized analogs with D-Trp7, D-Trp9, D-Trp10, D-pClPhe10, Nle11, Leu11, Ile11 and Met11, etc. Twenty-one/47 antagonists were superior in potency to that of Spantide, the best was [D-Arg1,D-Na1(5), D-Trp7,9,Nle11]-SP which required a 255-fold increase in SP concentration to give 50% of the maximum response at a concentration of 10(-5)M of the antagonist; this potency is ca. 5 times that of Spantide. For certain, but not all pairs of undecapeptides and truncated analogs, the undecapeptides may be significantly more potent than the truncated counterparts.

The heptapeptide methyl ester Phe-Asn-Glu-Asn-Met-Ala-Tyr-OMe covering the amino acid sequence of the region 213-219 of Escherichia Coli K88 ad protein fimbriae is synthesized using N alpha-t-butyloxycarbonyl-protection and benzyl groups for side-chain-protection. All condensation reactions are performed in 84-97% yield by preactivation of the protected amino acids by dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt), and reaction of the resulting active ester with amine in the presence of 4-methylmorpholine (NMM). A mechanism is proposed for the nitrile formation in the side-chain of activated asparagine, and the suppression of this side-reaction is investigated. The repetitive deprotection is performed in a mixture of trifluoroacetic acid (TFA), phenol and p-cresol to give the TFA salts in virtually quantitatively yields. The final deprotection of the heptapeptide is carried out in a mixture of 25% hydrogen fluoride (HF) and dimethyl sulfide (DMS) in an overall yield of 48%. The serological and conformational properties of the synthetic peptide are under investigation.