Ghosh I, Issac R, Chmielewski J
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Bioorg Med Chem. 1999 Jan;7(1):61-6. doi: 10.1016/s0968-0896(98)00214-4.
A beta-sheet peptide inhibitor, 2H10, has been developed that inhibits the dimerization of the transcription factor E47. Inhibition of E47 dimerization has been demonstrated to also inhibit the DNA binding of this transcription factor. Truncated peptides based on 2H10 have demonstrated that the beta-sheet content of these peptides directly correlates with their inhibitory properties. Individual residues within 2H10 were identified that were responsible for the beta-sheet secondary structure by employing an alanine replacement strategy. The beta-sheet character of the alanine mutants also correlated well with their inhibition of E47 DNA binding. These results provide further evidence that interactions between the interfacial peptide inhibitors of E47 and the transcription factor itself are mediated by a beta-sheet structure.
一种β-折叠肽抑制剂2H10已被开发出来，它能抑制转录因子E47的二聚化。E47二聚化的抑制已被证明也会抑制该转录因子与DNA的结合。基于2H10的截短肽表明，这些肽的β-折叠含量与其抑制特性直接相关。通过采用丙氨酸替代策略，确定了2H10中负责β-折叠二级结构的个别残基。丙氨酸突变体的β-折叠特性与其对E47与DNA结合的抑制也有很好的相关性。这些结果进一步证明，E47的界面肽抑制剂与转录因子本身之间的相互作用是由β-折叠结构介导的。
