Popp J L, Musza L L, Barrow C J, Rudewicz P J, Houck D R
Sterling Winthrop Pharmaceuticals Research Division, Collegeville, PA 19426-0900.
J Antibiot (Tokyo). 1994 Apr;47(4):411-9. doi: 10.7164/antibiotics.47.411.
WIN 64821 (1) is a substance P (SP) antagonist isolated from a fungal culture (Aspergillus sp., SC319). It is a symmetrical dimer biosynthesized from four aromatic amino acid molecules: each equivalent half of the dimer is constructed from one molecule of phenylalanine (Phe) and one molecule of tryptophan (Trp). Feeding analogs of Phe, Trp, and other amino acids to intact cells of SC319 has yielded 36 biosynthetic analogs of WIN 64821. The analogs fall into three categories: substitutions on the indoline ring, substitutions on the Phe-derived phenyl ring, and replacement of the phenyl ring by an aliphatic group. In addition, these directed biosynthesis experiments generated asymmetrical dimers (derived from three amino acids) and, often, symmetrical dimers (derived from two amino acids). The relative SP binding affinities of several analogs suggest involvement of both the indoline and phenyl moieties in SP receptor binding.
WIN 64821 (1) 是一种从真菌培养物（曲霉属，SC319）中分离出的P物质（SP）拮抗剂。它是一种由四个芳香族氨基酸分子生物合成的对称二聚体：二聚体的每个等效半体由一个苯丙氨酸（Phe）分子和一个色氨酸（Trp）分子构建而成。将Phe、Trp和其他氨基酸的类似物添加到SC319的完整细胞中，已产生了36种WIN 64821的生物合成类似物。这些类似物分为三类：吲哚啉环上的取代、Phe衍生苯环上的取代以及苯环被脂肪族基团取代。此外，这些定向生物合成实验产生了不对称二聚体（由三个氨基酸衍生），并且常常产生对称二聚体（由两个氨基酸衍生）。几种类似物的相对SP结合亲和力表明吲哚啉和苯基部分都参与了SP受体结合。
