Kiyoto Edo

The structure of neocarzinostatin chromophore possessing a novel bicyclo-[7,3,0]dodecadiyne system

Abstract The structure of the chromophore of an antitumor antibiotic neocarzinostatin has been elucidated as a bicycro[7,3,0]dodecadiyne system having naphthalenecarboxylic acid, aminosugar and ethylene carbonate units.

Distribution of carbon-11 labeled methamphetamine and the effect of its chronic administration in mice

[11C]Methamphetamine, a psychotropic agent, was synthesized by N-methylation of amphetamine with [11C]CH3 I in hopes that it could be applied in the near future to assist positron emission tomography (PET) in the imaging of its distribution in the human brain. The regional distribution of [11C]methamphetamine was investigated in the mice brain at various intervals after an intravenous (i.v.) injection. Radioactivity was higher in the hypothalamus, cortex, striatum and hippocampus. Furthermore, in chronically administered mice, the uptake of [11C]methamphetamine was higher in the striatum than those in other regions. The regional differences in the distribution of methamphetamine in the mice brain may enable the imaging of its distribution by PET using [11C]methamphetamine.

Proton NMR studies on the chromophore binding structure in neocarzinostatin complex

Abstract NMR studies indicatethe hydrophobic pocket formedby the internalfour-stand β-sheet of apoprotein bindsNCS-chr with the conformation in wich its naphthoate moiety sits on the bottom of the pocket and the aminosugar and the carbonate group face outwards.

Neocarzinostatin Chromophore: Structure and Mechanism of DNA Cleavage

Neocarzinostatin (NCS) is a member of a family of chromoprotein antitumor antibiotics. It consists of two noncovalently bound components, a labile chromophore component (NCS-chrom) with biological activities such as DNA cleavage and a protein component that stabilizes NCS-chrom. NCSchrom was the first of the enediyne antibiotics to be isolated and characterized. The chemical structure has been elucidated: a novel epoxybicyclo [7,3,01 dodecadienediyne system, an interconnecting highly unsaturated 12-member carbon ring subunit, bearing subunits 2-hydroxy-5-methyl-7-methoxyl1-naphthoate, 2,6-dideoxy-2-methylamino-galactose, and ethylene carbonate. The mechanism for the activation of NCS-chrom highlights one of the crucial roles of the thiol in the mechanism of action of NCS. Nucleophilic attack by a thiol results in a Bergman-type electronic rearrangement to form a biradical species that cleaves DNA by abstracting hydrogen atoms from the deoxyribose sugar. Moreover, another pathway for the thiol-independent mechanism of action of NCS-chrom has been proposed. In this mechanism, the spirolactone cumulene is stereoselectively generated via an intramolecular Michael addition at C-12 by the enolate anion of naphthoate of NCS-chrom, resulting in the formation of the biradical.

Improved production of a chromophore component of antitumor antibiotic neocarzinostatin (NCS) by addition of threonine in a chemically defined medium

Abstract Production in a chemically defined medium of a free chromophore component (free NCS-chr) of an antitumor antibiotic neocarzinostatin (NCS) by Streptomyces carzinostaticus var. F-41 was improved by the use of l -threonine or l -asparagine as a sole nitrogen source. Under the conditions established, the yield of free NCS-chr was comparable to that obtained in a control medium containing casamino acids.