Proteins with beta-(thienopyrrolyl)alanines as alternative chromophores and pharmaceutically active amino acids

Citation
N. Budisa et al., Proteins with beta-(thienopyrrolyl)alanines as alternative chromophores and pharmaceutically active amino acids, PROTEIN SCI, 10(7), 2001, pp. 1281-1292
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEIN SCIENCE
ISSN journal
0961-8368 → ACNP
Volume
10
Issue
7
Year of publication
2001
Pages
1281 - 1292
Database
ISI
SICI code
0961-8368(200107)10:7<1281:PWBAAC>2.0.ZU;2-A
Abstract
L-beta-(Thieno[3,2-b]pyrrolyl)alanine and L-beta-(thieno[2,3-b]pyrrolyl)ala nine are mutually isosteric and pharmaceutically active amino acids that mi mic tryptophan with the benzene ring in the indole moiety replaced by thiop hene. Sulfur as a heteroatom causes physicochemical changes in these trypto phan surrogates that bring about completely new properties not found in the indole moiety. These synthetic amino acids were incorporated into recombin ant proteins in response to the Trp UGG codons by fermentation in a Trp-aux otrophic Escherichia coli host strain using the selective pressure incorpor ation method. Related protein mutants expectedly retain the secondary struc ture of the native proteins but show significantly changed optical and ther modynamic properties. In this way, new spectral windows, fluorescence, pola rity, thermodynamics, or pharmacological properties are inserted into prote ins. Such an engineering approach by translational integration of synthetic amino acids with a priori defined properties, as shown in this study, prov ed to be a novel and useful tool for protein rational design.