Open AccessSequence-selective DNA recognition and enhanced cellular up-take by peptide–steroid conjugates
Author(s) -
Yara Ruiz García,
Abhishek Iyer,
Dorien Van Lysebetten,
Y. Vladimir Pabon,
Benoit Louage,
Małgorzata Honcharenko,
Bruno G. De Geest,
Smith Rjh,
Roger Strömberg,
Annemieke Madder
Publication year - 2015
Publication title -
chemical communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.837
H-Index - 333
eISSN - 1364-548X
pISSN - 1359-7345
DOI - 10.1039/c5cc07097j
Subject(s) - chemistry , click chemistry , peptide , conjugate , leucine zipper , steroid , cycloaddition , sequence (biology) , dna , combinatorial chemistry , deoxycholic acid , peptide sequence , biochemistry , biophysics , biology , hormone , bile acid , gene , catalysis , mathematical analysis , mathematics
Several GCN4 bZIP TF models have previously been designed and synthesized. However, the synthetic routes towards these constructs are typically tedious and difficult. We here describe the substitution of the Leucine zipper domain of the protein by a deoxycholic acid derivative appending the two GCN4 binding region peptides through an optimized double azide-alkyne cycloaddition click reaction. In addition to achieving sequence specific dsDNA binding, we have investigated the potential of these compounds to enter cells. Confocal microscopy and flow cytometry show the beneficial influence of the steroid on cell uptake. This unique synthetic model of the bZIP TF thus combines sequence specific dsDNA binding properties with enhanced cell-uptake. Given the unique properties of deoxycholic acid and the convergent nature of the synthesis, we believe this work represents a key achievement in the field of TF mimicry.
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