RT Journal Article
T1 Sequence‐Selective DNA Recognition with Peptide–Bisbenzamidine Conjugates
A1 Sánchez López, Mateo Isidro
A1 Vázquez Vázquez, Olalla
A1 Vázquez Sentís, Marco Eugenio
A1 Mascareñas Cid, José Luis
K1 DNA recognition
K1 Fluorescence
K1 Molecular recognition
K1 Olligonucleotides
K1 Peptides
AB Transcription factors (TFs) are specialized proteins that play a key role in the regulation of genetic expression. Their mechanism of action involves the interaction with specific DNA sequences, which usually takes place through specialized domains of the protein. However, achieving an efficient binding usually requires the presence of the full protein. This is the case for bZIP and zinc finger TF families, which cannot interact with their target sites when the DNA binding fragments are presented as isolated monomers. Herein it is demonstrated that the DNA binding of these monomeric peptides can be restored when conjugated to aza‐bisbenzamidines, which are readily accessible molecules that interact with A/T‐rich sites by insertion into their minor groove. Importantly, the fluorogenic properties of the aza‐benzamidine unit provide details of the DNA interaction that are eluded in electrophoresis mobility shift assays (EMSA). The hybrids based on the GCN4 bZIP protein preferentially bind to composite sequences containing tandem bisbenzamidine–GCN4 binding sites (TCAT⋅AAATT). Fluorescence reverse titrations show an interesting multiphasic profile consistent with the formation of competitive nonspecific complexes at low DNA/peptide ratios. On the other hand, the conjugate with the DNA binding domain of the zinc finger protein GAGA binds with high affinity (KD≈12 nM) and specificity to a composite AATTT⋅GAGA sequence containing both the bisbenzamidine and the TF consensus binding sites
PB Wiley
YR 2013
FD 2013
LK http://hdl.handle.net/10347/18484
UL http://hdl.handle.net/10347/18484
LA eng
NO Sánchez, M. I., Vázquez, O. , Vázquez, M. E. and Mascareñas, J. L. (2013), Sequence‐Selective DNA Recognition with Peptide–Bisbenzamidine Conjugates. Chem. Eur. J., 19: 9923-9929. doi:10.1002/chem.201300519
NO This is the peer reviewed version of the following article: Sánchez, M. I., Vázquez, O. , Vázquez, M. E. and Mascareñas, J. L. (2013), Sequence‐Selective DNA Recognition with Peptide–Bisbenzamidine Conjugates. Chem. Eur. J., 19: 9923-9929, which has been published in final form at https://doi.org/10.1002/chem.201300519. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions
NO We thank the financial support provided by the Spanish grants Consolider Ingenio 2010 (SAF2010‐20822‐C02, CTQ2009‐14431/BQU, CTQ2012‐31341, CSD2007‐00006), the Xunta de Galicia (GRC2010/12, INCITE09 209 084PR, PGIDIT08CSA‐047209PR). M.I.S. thanks the Ministerio de Educación, Cultura y Deporte for his PhD fellowship
DS Minerva
RD 29 abr 2026