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Click‐Chemistry‐Derived Tetracycline–Amino Acid Conjugates Exhibiting Exceptional Potency and Exclusive Recognition of the Reverse Tet Repressor
Author(s) -
Usai Igor,
Krueger Marcus,
Einsiedel Jürgen,
Hillen Wolfgang,
Gmeiner Peter
Publication year - 2010
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200900710
Subject(s) - tetr , click chemistry , chemistry , conjugate , combinatorial chemistry , cycloaddition , amino acid , stereochemistry , repressor , biochemistry , gene expression , gene , catalysis , mathematical analysis , mathematics
A click‐chemistry‐based synthesis of biologically active doxycycline–amino acid conjugates is described. Starting from 9‐aminodoxycycline derivatives and complementary functionalized amino acids, ligation was accomplished by copper(I)‐catalyzed azide–alkyne [3+2] cycloaddition (CuAAC). The final products were tested in a variety of TetR and revTetR systems, and the C‐terminally linked phenylalanine conjugate 12 c exhibited high selectivity for revTetR over TetR. Besides the unique property of the specific effector 12 c to effectively differentiate TetR and its reverse phenotype, the test compound proved to be almost devoid of any antibacterial activity; this will be highly beneficial for future applications to control gene expression in bacterial systems.