Neocarzinostatin derivatives and a process for manufacturing...

C - Chemistry – Metallurgy – 07 – K

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530/13

C07K 17/08 (2006.01) C07K 14/00 (2006.01)

Patent

CA 1241640

Abstract of the Disclosure Neocarzinostatin derivatives having excellent anticancer activity, which have the following formula (A) (SMA)-(NCS)-(SMA) (A) wherein (NCS) represents divalent neocarzinostatin residue in which one hydrogen atom is removed from each of the primary amino group in alanine residue at the N-terminal of neocarzinostatin and that in lysine residue at 20th position from the N-terminal of neocarzinostatin and (SMA) represents monovalent styrene-maleic acid copolymeric residue having a weight- average molecular weight of 800?2,500 and consisting of structural units of styrene residue (a) Image ; maleic acid residue (b) Image ; and a residue (c) having the following formula in which a hydroxyl group of one carboxyl group in the maleic acid residue is removed and link to be bonded to neocarzinostatin residue Image wherein the linkage of carbon atom in carbonyl group bonds to the neocarzinostatin residue. Said neocarzino- statin derivative is manufactured by reacting neo- carzinostatin in an aqueous medium with a large molar excess of powdery partially hydrolyzed styrene-maleic anhydride copolymer consisting of styrene residue; Image maleic acid residue; and Image maleic anhydride residue Image and having the particularly defined weight average molecular weight and number average molecular weight, and then subjecting the reaction product to gel filtration to isolate neocarzinostatin derivative.

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