Cyclodextrin-peptide conjugates for sequence specific DNA bindingElectronic supplementary information (ESI) available: Reaction conditions, RP-HPLC traces, ESI-MS, NMR spectra and EMSA studies. See DOI: 10.1039/c5ob00609k

Synthetic models of bZIP transcription factors have been developed with the capability of specific DNA recognition. Our design is based on the CuAAC mediated conjugation of basic region Leucine Zipper peptides to different derivatives of α, β and γ-cyclodextrins equipped with azide functionalities. Thorough optimization of reaction conditions allowed convergent and simultaneous conjugation of two long unprotected cationic peptides to cyclodextrin-bis azide derivatives. The resulting constructs were shown to specifically recognize their cognate DNA sequence with nM affinities. In comparison with previously developed TF models, the derivatives described here combine the enhanced DNA binding capabilities with an easy and convergent synthetic route. CD-peptide conjugates were synthesized via CuAAC. Though the CD cavity size was shown to influence the binding affinity of the compounds, all constructs recognize and bind the cognate CRE dsDNA.