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    • 7. 发明申请
    • METHOD FOR PRODUCING PEPTIDES
    • 生产肽的方法
    • WO1997048726A1
    • 1997-12-24
    • PCT/JP1997002097
    • 1997-06-19
    • TAKEDA CHEMICAL INDUSTRIES, LTD.HATANAKA, ChitoshiABE, YasuakiYAMANO, Mitsuhisa
    • TAKEDA CHEMICAL INDUSTRIES, LTD.
    • C07K07/23
    • C07K7/23Y02P20/55
    • A peptide of the formula (I): 5-oxo-Pro-R -Trp-Ser-R -R -R -Arg-Pro-R , wherein R represents His, Tyr, Trp or p-NH2-Phe, R represents Tyr or Phe, R represents an optionally substituted Gly or an optionally substituted alpha -D-amino acid residue, R represents Leu, Ile or Nle, R represents (1) Gly-NH-R , wherein R represents a hydrogen atom or an alkyl group which may optionally be substituted with a hydroxyl group, or (2) NH-R , wherein R represents a hydrogen atom, an alkyl group which may optionally be substituted with a hydroxyl group or an ureido group (-NH-CO-NH2), is produced advantageously in an industrial scale by reacting a peptide of the the formula (II): 5-oxo-Pro-R -Trp-Ser-R -R -OH, wherein R , R and R have the same meanings as defined above or its salts, with a peptide of the formula (III): H-R -R -Pro-R , wherein R and R have the same meaning as defined above and R represents Arg which has been protected or its salts, to produce a peptide of the formula (I'): 5-oxo-Pro-R -Trp-Ser-R -R -R -R -Pro-R , wherein R , R , R , R , R and R have the same meanings as defined above or its salt, and then subjecting thus obtained peptide (I') to a de-protecting group reaction.
    • 式(I)的肽:5-氧代-Pro-R 1 -Trp-Ser-R 2 -R 3 -R 4 -Arg-Pro-R 6,其中R R 1表示Tyr或Phe,R 3表示任选取代的Gly或任选取代的α-D-氨基酸残基,R 4表示His,Tyr,Trp或p-NH 2-Phe, 表示Leu,Ile或Nle,R 6表示(1)Gly-NH-R 7,其中R 7表示氢原子或可任选被羟基取代的烷基,或(2 )NH-R 8,其中R 8表示氢原子,可任选被羟基或脲基(-NH-CO-NH 2)取代的烷基,有利地以工业规模生产 通过使式(II)的肽:5-氧代-Pro-R 1 -Trp-Ser-R 2 -R 3 -OH反应,其中R 1,R 2和 R 3具有与上述相同的含义或其盐,与式(III)的肽:HR 4 -R 5 -Pro-R 6,其中R 4和R“ 6>具有与上述相同的含义,R 5表示被保护的Arg或 其盐,以产生式(I')的肽:5-氧代-Pro-R 1 -Trp-Ser-R 2 -R 3 -R 4 -R 5 - Pro-R 6,其中R 1,R 2,R 3,R 4,R 5和R 6具有与上述相同的含义或其盐,然后 将如此得到的肽(I')进行脱保护基反应。