Wurtz N R, Turner J M, Baird E E, Dervan P B
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Org Lett. 2001 Apr 19;3(8):1201-3. doi: 10.1021/ol0156796.
[structure: see text]. Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to those of many naturally occurring DNA binding proteins. A machine-assisted Fmoc solid phase synthesis of polyamides has been optimized to afford high stepwise coupling yields (>99%). Two monomer building blocks, Fmoc-Py acid and Fmoc-Im acid, were prepared in multigram scale. Cleavage by aminolysis followed by HPLC purification affords up to 200 mg quantities of polyamide with purities and yields greater than or equal to those reported using Boc chemistry. A broader set of reaction conditions will increase the number and complexity of minor groove binding polyamides which may be prepared and help ensure compatibility with many commercially available peptide synthesizers.
[结构：见正文]。含有N-甲基咪唑（Im）和N-甲基吡咯（Py）氨基酸的聚酰胺是合成配体，其对DNA的亲和力和特异性与许多天然存在的DNA结合蛋白相当。聚酰胺的机器辅助Fmoc固相合成已得到优化，以提供高的逐步偶联产率（>99%）。以多克规模制备了两种单体构建块，Fmoc-Py酸和Fmoc-Im酸。通过氨解裂解，然后进行HPLC纯化，可得到高达200 mg的聚酰胺，其纯度和产率大于或等于使用Boc化学方法报道的结果。更广泛的反应条件将增加可制备的小沟结合聚酰胺的数量和复杂性，并有助于确保与许多市售肽合成仪的兼容性。
