Folkers G, Prota A, Merz A
Department of Pharmacy, ETH Zürich.
Farmaco. 1995 Jun;50(6):449-54.
In rational drug design the study of protein-ligand-interactions is one of the most important approaches to get knowledge of SAR. On this study N2-Phenylthioguanines were synthesized by Schiemann reaction from thioguanine followed by a substitution of the fluorine by aniline-derivatives. The activity of these HSV1 TK inhibitors was determined by kinetic measurements of thymidine phosphorylation. The N2-Phenylthioguanines gave the same activity as the oxoanalogues. Interaction energies between thymidine and HSV1 TK were measured by microcalorimetry. Results of the measurement showed negative delta G and delta H values which indicates that the binding of the natural substrate occurs spontaneously and is enthalpy driven.
在合理药物设计中，蛋白质-配体相互作用的研究是获取构效关系知识的最重要方法之一。在这项研究中，通过席曼反应由硫鸟嘌呤合成了N2-苯基硫鸟嘌呤，随后用苯胺衍生物取代氟。这些单纯疱疹病毒1型胸苷激酶抑制剂的活性通过胸苷磷酸化的动力学测量来确定。N2-苯基硫鸟嘌呤的活性与氧类似物相同。通过微量热法测量了胸苷与单纯疱疹病毒1型胸苷激酶之间的相互作用能。测量结果显示吉布斯自由能变（ΔG）和焓变（ΔH）值为负，这表明天然底物的结合是自发发生的，且由焓驱动。
