Neocarcinostatine

Scheme 16.21. Activation of neocarcinostatin (thiol independent pathway see Ref. If for...

Chemical Name Neocarzinostatin (combination with apoprotein) Common Name Neocarcinostatin Neocarzinostatin K Zinostatin Chemical Abstracts Registry No. 9014-02-2... 

The cytotoxic neocarzinostatin (NCS) is a small protein (Mw 12 kD) associated with a low molecular weight chromophore. NCS is rapidly cleared by the kidney and its cytotoxicity is non-cell specific. To modify its disposition, two poly(styrene-co-maleic acid anhydride) copolymers (Mw 1,500) have been coupled to one molecule of NCS, to give styrene-maleic-anhydride-neocarcinostatin (SMANCS) systems. 

For almost 15 years, neocarcinostatin stood alone as an antibiotic with a unique pattern of DNA-damaging action. However, owing to an intensive search for other natural compounds with similar activity, several other antibiotics containing the enediyne fragment were found. Thus in 1987, almost simultaneously, esperamicin Aj 292 ° and calicheamicin y 293 ° were... 

Fig. 38. Expansion of the aliphatic region of a two-dimensional TOCSY spectrum of the 113-residue apoprotein of neocarcinostatin (NCS) with a mixing time of 70 ms. Examples of long side chain H spin qrstems fully assigned from the cross-peaks resulting from long-range homonuclear Hartmann-Hahn transfer are shown. Residues Pro 9 (below the diagonal) and Lys 20 (above the diagonal) are traced out. (Adapted from Remerowski et at., 1990, courtesy of the American Chemical Society.)...

Neocarcinostatin chromophore model Intramol. HR of an alkenyl bromide [175]... 

Neocarzinostatin, a polypeptide antibiotic from Streptomyces carzinostaticus with strong anticancer activity. Neocarcinostatin consists of an enediyne chromophore non-covalently associated to a peptide chain with 113 residues (Mr 10.7 kDa). Neocarzinostatin has potential importance for the therapy of leukemia and both stomach and pancreatic cancer [A. L. Smith, K. C. Nicolaou, J. Med. Chem. 1996, 39, 2103]. 

SMANCS (styrene maleic acid neocarcinostatin) soluble in Lipiodol as the chemoembolic agent, followed by Gelfoam. Matsui et al. (1993) reported that subsegmental chemoembolization with iodized oil and anticancer drugs followed by gelatin sponge particles or a mixture of iodized oil and absolute ethanol in 82 patient with nodular HCC (less than 4 cm in diameter, Childs classes A and B), yielded 1- and 4-year survival rates of 100% and 67%, respectively. 

F. Suzuki, T. Munakata, and H. Maeda, Interferon induction by SMANCS Polymer conjugated derivative of neocarcinostatin. Anticancer Res., 8,97-104,1988. 

K. Tatsumi and H. Nishioka, Effect of DNA repair systems on antibacterial and mutagenic activity of an antitumor protein, neocarcinostatin, Mutat. Res. 48, 195 (1977). 

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