Isernia C, Falcigno L, Macura S, Paolillo L, Pastore A L, Zanotti G
Second University of Naples, Environmental Sciences Faculty, Caserta, Italy.
J Pept Sci. 1996 Jan-Feb;2(1):3-13. doi: 10.1002/psc.44.
The evaluation of peptide structures in solution is made feasible by the combined use of two-dimensional NMR in the laboratory (NOESY) and rotating frames (ROESY), and by the use of molecular dynamics calculations. The present paper describes how both the NMR method and molecular dynamics calculations were applied to very rigid synthetic bicycle peptides that are analogues of natural amatoxins. The NMR theory, which allows the estimate of interatomic distances between interacting nuclei, is briefly discussed. The experimental data were compared with those of known solid-state structures. Three amatoxin analogues have been examined. Of these, one is biologically active (S-deoxo gamma[R] OH-Ile3-amaninamide) and its structure in the solid state has recently been worked out. The second and third analogues (S-dexo-Ile3-Ala5-amaninamide and S-deoxo-D-Ile3-amaninamide, respectively) are inactive and their solid-state structures are unknown. The data presented confirm the authors previous hypothesis that lack of biological activity of S-deoxo-Ile3-Ala5-amaninamide is due to the masking of the tryptophan ring by the methyl group of L-Ala and not to massive conformational changes of the analogue.
通过在实验室中联合使用二维核磁共振（NOESY）和旋转坐标系（ROESY）以及运用分子动力学计算，使得溶液中肽结构的评估成为可能。本文描述了核磁共振方法和分子动力学计算如何应用于与天然鹅膏毒素类似的非常刚性的合成双环肽。简要讨论了能够估算相互作用原子核之间原子间距离的核磁共振理论。将实验数据与已知固态结构的数据进行了比较。已对三种鹅膏毒素类似物进行了研究。其中一种具有生物活性（S-脱氧γ[R]OH-Ile3-鹅膏氨酸酰胺），其固态结构最近已被确定。另外两种类似物（分别为S-脱氧-Ile3-Ala5-鹅膏氨酸酰胺和S-脱氧-D-Ile3-鹅膏氨酸酰胺）无活性，其固态结构未知。所呈现的数据证实了作者之前的假设，即S-脱氧-Ile3-Ala5-鹅膏氨酸酰胺缺乏生物活性是由于L-Ala的甲基掩盖了色氨酸环，而非该类似物发生了大量构象变化。
