海洋海绵细胞生长抑制性环肽phakellistatin 1的分离与结构

Isolation and structure of the marine sponge cell growth inhibitory cyclic peptide phakellistatin 1.

作者信息

Pettit G R, Cichacz Z, Barkoczy J, Dorsaz A C, Herald D L, Williams M D, Doubek D L, Schmidt J M, Tackett L P, Brune D C

机构信息

Department of Chemistry, Arizona State University, Tempe 85287-1604.

出版信息

J Nat Prod. 1993 Feb;56(2):260-7. doi: 10.1021/np50092a011.

DOI:10.1021/np50092a011

PMID:8463798

Abstract

A new cell growth inhibitory (P-388 murine leukemia ED50 7.5 micrograms/ml) cycloheptapeptide designated phakellistatin 1 was isolated from two Indo-Pacific sponges, Phakellia costata and Stylotella aurantium. Structural elucidation was accomplished utilizing high field nmr, amino acid analyses, and mass spectral techniques (fab, tandem ms/ms), followed by chiral gas chromatographic procedures for absolute configuration assignments (all S-amino acid units). By these methods phakellistatin 1 [1] was found to be cyclo (Pro-Ile-Pro-Ile-Phe-Pro-Tyr), and this assignment was finally confirmed by an X-ray crystal structure determination.

摘要

从两种印度 - 太平洋海绵，即肋状扁海绵（Phakellia costata）和金色柱海绵（Stylotella aurantium）中分离出一种新的具有细胞生长抑制作用的环庚肽（P - 388小鼠白血病的半数有效剂量为7.5微克/毫升），命名为扁海绵抑肽素1。利用高场核磁共振、氨基酸分析和质谱技术（快原子轰击质谱、串联质谱/二级质谱）进行结构解析，随后采用手性气相色谱法确定绝对构型（所有氨基酸单元均为S型）。通过这些方法，发现扁海绵抑肽素1 [1]为环（脯氨酸 - 异亮氨酸 - 脯氨酸 - 异亮氨酸 - 苯丙氨酸 - 脯氨酸 - 酪氨酸），并且该结构归属最终通过X射线晶体结构测定得以证实。