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公开(公告)号:US5807979A
公开(公告)日:1998-09-15
申请号:US456424
申请日:1995-06-01
IPC分类号: A61K39/00 , C07K1/107 , C07K1/113 , C07K7/02 , C07K14/16 , C07K14/445 , C07K14/485 , G01N33/68 , C07K7/54 , C07K14/155
CPC分类号: C07K14/005 , C07K1/1075 , C07K1/113 , C07K14/445 , C07K14/485 , C07K7/02 , G01N33/6878 , A61K39/00 , C12N2740/16122
摘要: Methods for synthesizing three-dimensional stabilized peptides which mimic the three-dimensional configuration of the active site of a natural, biologically active protein are carried out by (1) noting the three-dimensional configuration of the active site of a known biologically active protein (2) noting the amino acid sequence and the hydrogen bonds existing between amino acids which hydrogen bonds are capable of maintaining the three-dimensional configuration of the active site and (3) producing a synthetic three-dimensional peptide to mimic the structure of the active site. The synthetic peptide is synthesized so as to have the same or a similar amino acid sequence to the amino acid sequence of the active site of the biologically active polypeptide but with the stabilizing hydrogen bonds being replaced by a bridging divalent radical selected from the group of --(N)--C(CH.sub.3).dbd.N(H.sup.+)--CH.sub.2 --(N)--; --(N)--C(CH.sub.3).dbd.N(H.sup.+)--CH.sub.2 --CH.sub.2 --(N)--; and --(N)--N.dbd.CH--CH.sub.2 --CH.sub.2 --CH.sub.2 --(C)--. The stabilized three-dimensional peptide obtained is then isolated from the reaction mixture. The invention makes it possible to produce a wide range of biologically active compounds which have stable three-dimensional structures which allow the compounds to be used to obtain, for example, stabilized three-dimensional peptides which mimic the antigenic sites on viral envelopes which are useful as vaccines.
摘要翻译: 用于合成模拟天然生物活性蛋白质的活性位点的三维构型的三维稳定肽的方法通过以下方式进行:(1)注意已知生物活性蛋白质的活性位点的三维构型( 2)注意氨基酸序列和氢键之间存在的氨基酸之间的氢键能够维持活性位点的三维构型,(3)产生合成的三维肽以模拟活性位点的结构 。 合成肽被合成以具有与生物活性多肽的活性位点的氨基酸序列相同或相似的氨基酸序列,但是稳定氢键被选自以下的桥连二价基团取代: (N)-C(CH 3)= N(H +) - CH 2 - (N) - ; - (N)-C(CH 3)= N(H +) - CH 2 -CH 2 - (N) - ; 和 - (N)-N = CH-CH 2 -CH 2 -CH 2 - (C) - 。 然后从反应混合物中分离得到的稳定化的三维肽。 本发明使得可以生产出具有稳定三维结构的广泛范围的生物活性化合物,其允许化合物用于获得例如稳定的三维肽,其模拟病毒包膜上的抗原位点,其是有用的 作为疫苗。