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WIN 64821, a novel neurokinin antagonist produced by an Aspergillus sp. III. Biosynthetic analogs

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journal contribution
posted on 1994-04-01, 00:00 authored by J L Popp, L L Musza, Colin BarrowColin Barrow, P J Rudewicz, D R Houck
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.

History

Journal

Journal of antibiotics

Volume

47

Issue

4

Pagination

411 - 419

Publisher

Japan Antibiotics Research Association

Location

Tokyo, Japan

ISSN

0021-8820

eISSN

1881-1469

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

1994, Japan Antibiotics Research Association