Neocarzinostatin, conjugate

For this reason, although the first polymer-protein conjugates used clinically were streptokinase conjugated to dextran [8] and neocarzinostatins linked to succinic acid-co-maleic anhydride [5], from the 1980s onwards PEG became the polymer of choice, and all products that subsequently appeared on the market were based on this reagent. 

Nagata, R. Yamanaka, H. Okazaki, E. Saito, I. Biradical formation from acyclic conjugated eneyne-allene system related to neocarzinostatin and esperamicin-calichemicin, Tetrahedron Lett. 1989, 30,4995-4998. 

Myers, A.G. Kuo, E.Y. Finney, N.S. Thermal generation of alpha,3-dehydrotoluene from (Z)-l,2,4-heptatricn-6-ync. J. Am. Chem. Soc. 1989, 111, 8057-8058 Nagata, R. Yamanaka, H. Okazaki, E. Saito, I. Biradical formation from acyclic conjugated eneyne-allene system related to neocarzinostatin and esperamicin-calichemicin. Tetrahedron Lett. 1989, 30, 4995 998. 

Yamamoto H, Mild T, Oda T, et al. Reduced bone marrow toxicity of neocarzinostatin by conjugation with divinyl ether-mialeic acid copolymer. Eur J Cancer 1990 26 253-260. 

Martin s sulfurane has been used to prepare a variety of cyclopentenes for use in the total syntheses of complex natural products. Myers effectively employed the title reagent to prepare synthetic intermediates for use in his total synthesis of the neocarzinostatin chromophore.43 (For dehydrations to yield alkenes in the nine-membered ring of this compound, see Section 3.7.5.4.) One example is reaction of tertiary alcohol 86 to furnish alkene 87 in 93% yield. In Phillips s total synthesis of cylindramide A, he employed a conjugate addition-reduction-elimination sequence (88—>89) to generate the... 

Another polyvinylic prodrug, SMANCS (Fig. 34.3), is a conjugate of a low molecular weight styrene maleic anhydride copolymer (SMA, 1.6 kDa) and neocarzinostatin (NCS). It is already marketed in Japan for the treatment of hepatocellular carcinoma. 

Maeda H, Takeshita J, Kanamaru R. A lipophilic derivative of neocarzinostatin. A polymer conjugation of an antitumor protein antibiotic. Int J Pet Protein Res 1979 14 81—87. 

Initially, Maeda et al. conjugated an antitumor protein neocarzinostatin (NCS, MW 12 kDa) with copolymer of styrene-maleic acid half-w-butylate (SMA) [59-61]. The eonjugation of protein (NCS) with SMA called SMANCS... 

Maeda H, Ueda M, Morinaga T, Matsumoto T. Conjugation of poly(styrene-co-maleic acid) derivatives to the antitumor protein neocarzinostatin Pronounced improvements in pharmacological properties. J Med Chem 1985 28 455-461. 

Oda T, Maeda H. Binding to and internalization by cultured cells of neocarzinostatin and enhancement of its actions by conjugation with hpophihc styrene-maleic acid copolymer. Cancer Res 1987 47 3206 3211. 

Neocarzinostatin 301, first reported by Ishida and coworkers in 1965, is produced by S. carzinostaticus ATCC 15994 and is a 1 1 noncovalently associated mixture of a protein component, apoprotein, and a chromophoric molecule [297]. The mixture was separated somewhat later into its component parts and eventually characterized structurally. The chromophoric component was shown in 1985 to have the nine-membered polyeneyne skeleton 301 [298]. The apoprotein has been characterized as a 113 amino acid polypeptide based upon the gene base sequence and apoprotein crystal structure [299, 300]. The three-dimensional solution structure of intact neocarzinostatin was determined using 2D NMR techniques [301], and the crystal structure of holo-neocarzinostatin was reported in the same year [302]. The antibiotic 301 showed potent antitumor activity against a wide range of tumors and a poly(styrene-co-maleic acid)-301 conjugate was approved in Japan and has been marketed for use against hepatoma since 1994 [303]. 

SMANCS Poly(styrene-co-maleic acid-half-n-butylate) conjugated with neocarzinostatin Tax Paclitaxel, also known as Taxol... 

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