| Summary: | 碩士 === 東海大學 === 化學系 === 98 === Id1 proteins, inhibitors of differentiation or DNA binding, act as dominant negative antagonists of the basic helix–loop–helix (bHLH) family of transcription factors, which play an important role in cellular development, proliferation, and differentiation. The mechanism of Id proteins is to antagonize basic helix-loop-helix proteins, they bind as dominant-negative HLH proteins by forming high affinity heterodimers with other bHLH proteins, thereby preventing them from binding to DNA and inhibiting transcription of differentiation associated genes.The goal of this study is to design and synthesize N- or C-terminal deleted analogs of peptide 3C with high affinity for Id1 protein in order to interrupt the interactions among Id1, MyoD, and other bHLH DNA-binding proteins and to inhibit the proliferation of cancer cells. Affinity of each peptide for Id1 HLH domain was determined by surface plasmon resonance (SPR) technology. The secondary structure of each peptide was studied by circular dichroism (CD) spectroscopy. Biological effects of each peptide in breast cancer cell (MCF-7) was analyzed. Results demonstrated that the peptide 3C and peptide 3C-CtD4 showed high affinity for Id1 and the equilibrium dissociation constant (KD) were 3.16 μM and 2.77 μM, respectively. Comparison of the secondary structures of peptides, we found that the ratios of α-helix structure in the deleted peptides were different. Results of MTT assay demonstrated that treatment of MCF-7 with these peptides did not exhibit antiproliferation effects in cancer cells. We suggest that further modifications of amino acid residues in peptides 3C and 3C-CtD4 and further assay of peptides for their effects in other cancer cells may enhance the antiproliferative potency and the specificity of peptides. In summary, peptides 3C and 3C-CtD4 are promising lead compounds for the development of peptidic antagonists or anticancer agents.
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