Sequence-selective DNA recognition and enhanced cellular up-take by peptide-steroid conjugates

被引：7

作者：

Garcia, Yara Ruiz ^{[1
]}

Iyer, Abhishek ^{[1
]}

Van Lysebetten, Dorien ^{[1
]}

Pabon, Y. Vladimir ^{[2
]}

Louage, Benoit ^{[3
]}

Honcharenko, Malgorzata ^{[4
]}

De Geest, Bruno G. ^{[3
]}

Smith, C. I. Edvard ^{[2
]}

Stromberg, Roger ^{[4
]}

Madder, Annemieke ^{[1
]}

机构：

[1] Univ Ghent, Dept Organ & Macromol Chem, Organ & Biomimet Chem Res Grp, B-9000 Ghent, Belgium

[2] Karolinska Univ Hosp Huddinge, Dept Lab Med, Clin Res Ctr, SE-14186 Stockholm, Sweden

[3] Univ Ghent, Dept Pharmaceut, B-9000 Ghent, Belgium

[4] Karolinska Inst, Dept Biosci & Nutr BioNut, S-14183 Stockholm, Sweden

来源：

CHEMICAL COMMUNICATIONS | 2015年 / 51卷 / 99期

基金：

瑞典研究理事会;

关键词：

TRANSCRIPTION FACTOR; SOLID-PHASE; BINDING; PROTEIN; CARRIERS; DIMER;

D O I：

10.1039/c5cc07097j

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：17552 / 17555

页数：4

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