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S Sano

Publications and source records attributed to S Sano.

At least 199 records · Page 11Linked to original sources
PubMed1987

OF4949, new inhibitors of aminopeptidase B. IV. Effects of OF4949 and its derivatives on enzyme systems.

OF4949-I and II inhibited aminopeptidase B from Ehrlich ascites carcinoma in a competitive way and the Ki value for both against L-arginine-beta-naphthylamide was 8 X 10(-9) M. Inhibition by I and II of various exopeptidases and endopeptidases was examined. OF4949-I and II both strongly inhibited leucine aminopeptidase and enkephalin-degrading aminopeptidase; I also inhibited enkephalinase B. The inhibitory effects of various derivatives of I and II on aminopeptidase B activity, showed that the terminal amino and carboxamide groups are essential for activity.

Aminopeptidases↗
PubMed1987

OF4949, new inhibitors of aminopeptidase B. V. Effect on the murine immune system.

OF4949-I inhibited the growth of the solid form of IMC carcinoma and protected against pulmonary metastases of Lewis lung carcinoma. It also augmented the cytostatic activity of mouse peritoneal macrophages, the natural killer activity, and the antibody-dependent cell-mediated cytotoxicity of mouse spleen cells. This substance was not cytotoxic to cultured tumor or normal cells even at high concentrations. These results suggest that a cell-mediated immune response stimulated by this compound might account for its antitumor activity.

Aminopeptidases↗
PubMed1987

[Porphyria].

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Heme↗
PubMed1986

Mechanism of DNA cleavage induced by sodium chromate(VI) in the presence of hydrogen peroxide.

Reactivities of chromium compounds with DNA were investigated by the DNA sequencing technique using 32P 5'-end-labeled DNA fragments, and the reaction mechanism was investigated by ESR spectroscopy. Incubation of double-stranded DNA with sodium chromate(VI) plus hydrogen peroxide or potassium tetraperoxochromate(V) led to the cleavage at the position of every base, particularly of guanine. Even without piperidine, the formation of oligonucleotides was observed, suggesting the breakage of the deoxyribose-phosphate backbone. ESR studies using hydroxyl radical traps demonstrated that hydroxyl radical is generated both during the reaction of sodium chromate(VI) with hydrogen peroxide and the decomposition of potassium tetraperoxochromate(V), and that hydroxyl radical reacts significantly not only with mononucleotides but also with deoxyribose 5-phosphate. ESR studies using a singlet oxygen trap demonstrated that singlet oxygen is also generated both by the same reaction and decomposition, and reacts significantly with deoxyguanylate, but scarcely reacts with other mononucleotides. Furthermore, ESR studies suggested that tetraperoxochromate(V) is formed by the reaction of sodium chromate(VI) with hydrogen peroxide. These results indicate that sodium chromate(VI) reacts with hydrogen peroxide to form tetraperoxochromate(V), leading to the production of the hydroxyl radical, which causes every base alteration and deoxyribose-phosphate backbone breakage. In addition, sodium chromate(VI) plus hydrogen peroxide generates singlet oxygen, which subsequently oxidizes the guanine residue. The mechanism by which both hydroxyl radical and singlet oxygen are generated during the reaction of sodium chromate(VI) with hydrogen peroxide was presented. Finally, the possibility that this reaction may be one of the primary reactions of carcinogenesis induced by chromate(VI) is discussed.

Chromates↗
PubMed1986

Photodynamic guanine modification by hematoporphyrin is specific for single-stranded DNA with singlet oxygen as a mediator.

Photodynamic modification of DNA by hematoporphyrin (Hp) was characterized by the DNA sequencing technique using 32P-labeled DNA fragments, and the reaction mechanism was investigated by ESR spectroscopy. Mild photodynamic treatment of single-stranded DNA with Hp induced an alteration of guanine residues, and subsequent treatment with piperidine led to chain cleavages at each guanine residue. On the other hand, methylene blue plus light modified the guanine residues in both single-stranded and double-stranded DNA. ESR studies using 2,2,6,6-tetramethylpiperidine and 2,2,6,6-tetramethyl-4-piperidone as singlet oxygen traps demonstrated that Hp plus light produced almost the same amount of singlet oxygen as methylene blue plus light and that the photochemically generated singlet oxygen reacts significantly with guanylate but only slightly with other mononucleotides. An ESR spin destruction method revealed that photoexcited Hp generated porphyrin radical, but guanylate did not react with this radical. These results indicate that photoexcited Hp reacts with oxygen to generate singlet oxygen which oxidizes the guanine residues of single-stranded DNA and that the difference in photoreactivities of DNA with Hp and methylene blue may be explained in terms of the structural difference in their intercalating abilities.

DNA Restriction Enzymes↗
PubMed1986

On the mechanism of the chemical and enzymic oxygenations of alpha-oxyprotohemin IX to Fe.biliverdin IX alpha.

alpha-Oxyprotohemin IX, an early intermediate in heme catabolism, was synthesized and its autoxidation to biliverdin IX alpha was studied. In anaerobic aqueous pyridine, alpha-oxyprotohemin (hexacoordinated) underwent autoreduction to yield an Fe(II) alpha-oxyprotoporphyrin pi-neutral radical bis(pyridine) complex, which reacted with an equimolar amount of dioxygen to give pyridine.verdohemochrome IX alpha and CO in 75-80% yield via an intermediate with an absorption maximum at 893 nm. Verdohemochrome IX alpha did not react with further dioxygen. Reconstituted apomyoglobin.alpha-oxyprotohemin IX complex (pentacoordinated) reacted with an equimolar amount of dioxygen to form an Fe(II) oxyporphyrin pi-neutral radical intermediate, which rearranged to a green compound (lambda max 660 and 704 nm) with elision of CO. The green product, which is probably an apomyoglobin.verdoheme pi-radical complex, reacted with another equimolar amount of dioxygen to give Fe(III).biliverdin IX alpha. Demetallation of this gave biliverdin IX alpha in overall yield of 70-75%. These results indicate that the sequence of oxyheme autoxidation in the presence of apomyoglobin is alpha-oxyprotoheme IX O2----CO----verdohemochrome IX alpha pi-radical O2----Fe(III).biliverdin IX alpha. A similar mechanism may prevail in vivo. The hexa- and pentacoordinated Fe(II) pi-radical form of the oxyporphyrin is crucial in triggering the autoxidation of the complex to verdohemochrome IX alpha. Further oxygenation of verdohemochrome IX alpha to Fe(III).biliverdin IX alpha occurred only in the pentacoordinated apomyoglobin.verdoheme Fe(II) complex.

Apoproteins↗
PubMed1986

OF4949, new inhibitors of aminopeptidase B. I. Taxonomy, fermentation, isolation and characterization.

New aminopeptidase B inhibitors that we named OF4949-I, II, III and IV were isolated from the culture broth of a fungus, Penicillium rugulosum OF4949. The molecular formula of I was C23H26N4O8 and that of II, C22H24O8, judging from elemental analysis and secondary ion mass spectrometry. The concentrations of I, II, III and IV required for 50% inhibition of aminopeptidase, using Ehrlich ascites carcinoma cells as the source of the enzyme, were 0.0054, 0.0048, 3.4 and 1.7 micrograms/ml, respectively. Components I and II augmented delayed-type hypersensitivity in mice to sheep red blood cells.

Aminopeptidases↗
PubMed1986

OF4949, new inhibitors of aminopeptidase B. II. Elucidation of structure.

The structures of OF4949-I, II, III and IV were identified by analysis of the products of their chemical degradation and by 1H NMR, 13C NMR, and mass spectrometry. These compounds were new cyclic peptides containing diphenyl ether as a chromophore. OF4949-I had two amino acids, beta-hydroxy-L-asparagine and 4-methylisodityrosine. The structural differences between I and II and between III and IV lay solely in the diphenyl ether moiety; the phenolic hydroxyl group in II and IV was methylated in I and III. OF4949-III and IV contained L-asparagine instead of the beta-hydroxy-L-asparagine moiety of I and II.

Aminopeptidases↗
PubMed1986

OF4949, new inhibitors of aminopeptidase B. III. Biosynthesis.

To elevate production of OF4949 by Penicillium rugulosum OF4949 and to elucidate the pathway of its biosynthesis, mutants were selected on the basis of their resistance to growth inhibition by phenylalanine analogs. A mutant resistant to m-fluorophenylalanine, strain No. M414, had 3-fold the production of the parent. In a study of the biosynthesis of OF4949-I and II, several 14C-labeled compounds were examined as possible precursors of OF4949. L-[14C]Tyrosine and L-[14C]asparagine were incorporated efficiently. Most of the radioactivity of L-[14C]tyrosine was found in the 4-methylisodityrosine (B2) or isodityrosine (B1) moieties, and that of L-[14C]asparagine was in the beta-hydroxyasparagine moiety.

Aminopeptidases↗
PubMed1986

Demonstration of intratumoral infiltration of tumor-specific Lyt-1+2- T cells mediating delayed-type hypersensitivity response and in vivo protective immunity.

The present study demonstrates the intratumoral infiltration of lymphocytes mediating anti-tumor delayed-type-hypersensitivity (DTH) responses as well as in vivo protective immunity. The surface phenotype and tumor specificity of these effector lymphocytes were determined. X5563 tumor-infiltrating lymphoid cells were obtained from the tumor mass of syngeneic C3H/HeN mice 2 weeks after the intradermal inoculation of 10(6) viable X5563 tumor cells. These lymphoid cells consisted of Thy-1-positive (29-35%), surface immunoglobulin-positive (16-29%), large granule-positive (15-25%) and esterase-staining-positive (10-20%) cells. They were tested for anti-X5563 DTH responses by utilizing a local adoptive transfer system and for tumor-neutralizing activity in a Winn assay. The results indicate that X5563 tumor-infiltrating lymphoid cells exhibited appreciable anti-X5563 DTH responses and conveyed complete protection against the tumor. Treatment of these lymphoid cells with anti-Thy-1.2 or anti-Lyt antibodies plus complement revealed that the in vivo anti-tumor immune responses were mediated predominantly by a Lyt-1+2- T cell subset. Such Lyt-1+2- T cell-mediated immunity was tumor-specific, since X5563-infiltrating and syngeneic MH134 hepatoma-infiltrating cells exhibited DTH response and tumor-neutralizing activity selectively against the respective tumor cell types. Thus, these results indicate that tumor-specific in vivo-protective Lyt-1+2- T cells infiltrate into the tumor mass. The results are discussed in the context of 1) the interrelation of DTH responses and the tumor protection mediated by the Lyt-1+2- T cell subset and 2) possible cellular interactions between Lyt-1+2- T cells and co-existing nonspecific tumoricidal effector cells such as macrophages.

Animals↗