Inhibition of protein degradation in living cells

专利名称：Inhibition of protein degradation in living

cells with dipeptides

发明人：Rohan T. Baker,David K. Gonda,Alexander

Varshavsky

申请号：US08/230453申请日：19940420公开号：US05766927A公开日：19980616

摘要：The half-life of a Type I, II and III non-compartmentalized intracellular proteinsis increased in living eukaryotic cells by contacting the cells with a regulator having anamino-terminal amino acid residue which is the same or similar to the amino-terminalresidue of the intracellular protein. The regulator is a dipeptide, a small polypeptide or acarboxyl-terminal derivative of an amino acid. The dipeptide or small polypeptide has anN-terminal amino acid residue which is Arg, Lys or His for the Type I protein, Phe, Leu,Trp, Tyr or Ile for the Type II protein and Ala, Ser or Thr for the Type III protein. Thecarboxyl- terminal derivative of an amino acid may be an amino acid modified at its C-terminus by the addition of a group selected from methyl, ethyl, propyl, butyl andisobutyl. The amino acid modified is the N-terminal amino acid residue of the dipeptide orsmall polypeptide for the respective Type I, II and III proteins. Compositions may beformed containing the regulator for contacting with the cells. Increasing the half-life ofintracellular protein with the regulator may be used for treating diseases resulting froman abnormal breakdown of a desired protein, and for enhancing in vivo production of adesired protein.

申请人：MASSACHUSETTS INSTITUTE OF TECHNOLOGY

代理人：Kevin M. Farrell

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