Pennington M W, Zadenberg I, Byrnes M E, Norton R S, Kem W R
Bachem Bioscience Inc., Department of Peptide Chemistry, Philadelphia, Pennsylvania.
Int J Pept Protein Res. 1994 May;43(5):463-70. doi: 10.1111/j.1399-3011.1994.tb00545.x.
The sea anemone polypeptide anthopleurin-A (AP-A) at nanomolar concentrations enhances myocardial contractility without affecting automaticity. It has a therapeutic index higher than that of the digitalis glycosides, and may serve as a molecular model for designing a new class of inotropic drugs acting on the myocardial Na channel at site 3. AP-A is a 49 residue peptide crosslinked by three disulfide bonds; its tertiary structure has been determined by NMR. Here we report the solid-phase synthesis of this polypeptide. Synthetic AP-A displayed CD and NMR spectra identical with those of the natural toxin; it possessed 94 +/- 15% of the inotropic activity of natural AP-A. Therefore, it is feasible to prepare various type 1 sea anemone toxin analogs by solid-phase chemical synthesis in order to identify side chains important for peptide folding and interaction with sodium channels.
海葵多肽海葵素-A（AP-A）在纳摩尔浓度下可增强心肌收缩力而不影响自律性。它的治疗指数高于洋地黄糖苷，可作为设计一类作用于心肌钠通道3位点的新型强心药物的分子模型。AP-A是一种由三个二硫键交联的49个氨基酸残基的肽；其三级结构已通过核磁共振确定。在此我们报道该多肽的固相合成。合成的AP-A显示出与天然毒素相同的圆二色光谱和核磁共振光谱；它具有天然AP-A 94±15%的强心活性。因此，通过固相化学合成制备各种1型海葵毒素类似物以确定对肽折叠和与钠通道相互作用重要的侧链是可行的。
