RT Journal Article
T1 Fluorescence-Labeled Bis-benzamidines as Fluorogenic DNA Minor-Groove Binders: Photophysics and Binding Dynamics
A1 Bordello Malde, Jorge
A1 Sánchez López, Mateo Isidro
A1 Vázquez Sentís, Marco Eugenio
A1 Mascareñas Cid, José Luis
A1 Al-Soufi, Wajih
A1 Novo, Mercedes
K1 DNA minor-groove binder
K1 DNA recognition
K1 Fluorescence correlation spectroscopy
K1 Photophysics
K1 Reaction dynamics
AB In recent decades there has been great interest in the design of highly sensitive sequence-specific DNA binders. The eligibility of the binder depends on the magnitude of the fluorescence increase upon binding, related to its photophysics, and on its affinity and specificity, which is, in turn, determined by the dynamics of the binding process. Therefore, progress in the design of DNA binders requires both thorough photophysical studies and precise determination of the association and dissociation rate constants involved. We have studied two bis-benzamidine (BBA) derivatives labeled by linkers of various lengths with the dye Oregon Green (OG). These fluorogenic binders show a dramatic fluorescence enhancement upon binding to the minor groove of double-stranded (ds) DNA, as well as significant improvement in their sequence specificity versus the parent BBA, although with decreased affinity constants. Detailed photophysical analysis shows that static and dynamic quenching of the OG fluorescence by BBA through photoinduced electron transfer is suppressed upon insertion of BBA into the minor groove of DNA. Fluorescence correlation spectroscopy yields precise dynamic rate constants that prove that the association process of these fluorogenic binders to dsDNA is very similar to that of BBA alone and that their lower affinity is mainly a consequence of their weaker attachment to the minor groove and the resultant faster dissociation process. The conclusions of this study will allow us to go one step further in the design of new DNA binders with tunable fluorescence and binding properties
PB WILEY-VCH Verlag GmbH
SN 0947-6539
YR 2014
FD 2014-11-21
LK http://hdl.handle.net/10347/12290
UL http://hdl.handle.net/10347/12290
LA eng
NO Bordello, J., Sánchez, M. I., Vázquez, M. E., Mascareñas, J. L., Al-Soufi, W. and Novo, M. (2015), Fluorescence-Labeled Bis-benzamidines as Fluorogenic DNA Minor-Groove Binders: Photophysics and Binding Dynamics. Chem. Eur. J., 21: 1609–1619. doi: 10.1002/chem.201404926
NO NOTICE: This is the peer reviewed version of the following article: Bordello, J., Sánchez, M. I., Vázquez, M. E., Mascareñas, J. L., Al-Soufi, W. and Novo, M. (2015), Fluorescence-Labeled Bis-benzamidines as Fluorogenic DNA Minor-Groove Binders: Photophysics and Binding Dynamics. Chem. Eur. J., 21: 1609–1619 [doi: 10.1002/chem.201404926]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for self-archiving.
NO J.B. and M.I.S thank the Spanish MCINN for their researchscholarships. The authors are thankful for financial support fromSpanish grants (CTQ2010-21369, SAF2013-41943-R andCTQ2012-31341), the Xunta de Galicia (GPC2013/052,GRC2013-041, CN 2012/314), the ERDF, and the EuropeanResearch Council (Advanced Grant Nº 340055). Support ofCOST Actions CM1105 and CM1306 and the orfeo-cinqa network is also kindly acknowledged
DS Minerva
RD 22 abr 2026