Ladame Sylvain, Schouten James A, Stuart John, Roldan Jose, Neidle Stephen, Balasubramanian Shankar
University Chemical Laboratory, University of Cambridge, UK.
Org Biomol Chem. 2004 Oct 21;2(20):2925-31. doi: 10.1039/B409698C. Epub 2004 Sep 20.
3,6-Bis-peptide acridine and acridone conjugates have been designed and synthesised to selectively interact with G-quadruplex DNA. The ligand properties are peptide sequence dependent, the highest discrimination being obtained with the FRHR tetrapeptide (up to >50-fold specificity). Molecular modeling studies have helped us rationalise the data and suggest that human telomeric quadruplex DNA can readily accommodate tetrapeptides, and furthermore that FRHR contributes to stabilization of the complex by non-bonded interactions within the TTA loop pockets of the quadruplex. These studies indicate that targeting distinct features of a G-quadruplex with hybrid molecules is a promising strategy for discriminating between quadruplex and duplex DNA.
已设计并合成了3,6 - 双肽吖啶和吖啶酮共轭物，使其与G - 四链体DNA选择性相互作用。配体性质取决于肽序列，使用FRHR四肽可获得最高的区分度（特异性高达50倍以上）。分子建模研究有助于我们对数据进行合理化分析，并表明人类端粒四链体DNA能够轻松容纳四肽，此外，FRHR通过四链体TTA环口袋内的非键相互作用有助于复合物的稳定。这些研究表明，用杂合分子靶向G - 四链体的不同特征是区分四链体和双链DNA的一种有前景的策略。
