Department of Chemistry Graduate School of Science, Kyoto University Kitashitakawa-oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.
Institute for Integrated Cell-Material Science (ICeMS), Kyoto University, Yoshida-ushinomiyacho Sakyo-ku, Kyoto, 606-8501, Japan.
Chembiochem. 2022 Jul 19;23(14):e202200124. doi: 10.1002/cbic.202200124. Epub 2022 Jun 9.
Pyrrole-imidazole polyamides (PIPs) bind to double-stranded DNA (dsDNA) with varied sequence selectivity. We synthesized linear PIPs that can bind to narrow minor grooves of polypurine/polypyrimidine sequences and target long recognition sequences but have lower molecular weights than commonly used hairpin PIPs. We modified the N-terminus of linear PIPs using several groups, including β-alanine extension and acetyl capping. Melting curve analysis of dsDNA demonstrated that cationic modifications improved the binding affinity of the PIPs to the targeted dsDNA. In addition, circular dichroism assays revealed the characteristic spectra depending on the binding stoichiometry of the N-cationic linear PIP and dsDNA (1 : 1, monomeric; 2 : 1, dimeric). Surface plasmon resonance assays confirmed the high binding affinities of linear PIPs. These findings may aid in the design of effective linear PIPs.
吡咯并咪唑多聚体（PIPs）与双链 DNA（dsDNA）结合具有不同的序列选择性。我们合成了可以与富含嘌呤/嘧啶序列的狭窄小沟结合并靶向长识别序列的线性 PIPs，但分子量低于常用的发夹 PIPs。我们使用几种基团修饰了线性 PIPs 的 N 端，包括β-丙氨酸延伸和乙酰化封端。dsDNA 的融解曲线分析表明，阳离子修饰提高了 PIP 与靶向 dsDNA 的结合亲和力。此外，圆二色性分析显示，N-阳离子线性 PIP 和 dsDNA 的结合比例（1:1，单体；2:1，二聚体）取决于结合化学计量比。表面等离子体共振分析证实了线性 PIPs 的高结合亲和力。这些发现可能有助于设计有效的线性 PIPs。
