Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines
Abstract
:1. Introduction
2. Results
2.1. UV-Thermal Melting Screening (Tm)
Compound/Drug:DNA Ratio | Tel22 | AATT duplex | ||||||
---|---|---|---|---|---|---|---|---|
1:1 | 2:1 | 4:1 | 6:1 | 1:1 | 2:1 | 4:1 | 6:1 | |
24 | 2 | 4 | 9 | 14 | 0 | 1 | 1 | 2 |
a | - | 2.1 | 4.6 | 8.7 | 0 | 0 | 0 | 0 |
25 | 1 | 1 | 1 | 0 | ND | |||
26 | 1 | 2 | 4 | 11 | 0 | 2 | 2 | 2 |
27 | 2 | 1 | 1 | 1 | ND | |||
28 | 1 | 1 | 3 | 7 | 1 | 1 | 2 | 3 |
29 | 3 | 8 | 12 | 16 | 0 | 1 | 1 | 2 |
30 | 3 | 7 | 15 | 19 | 0 | 0 | 1 | 1 |
b | - | 3.1 | 8.9 | 13.2 | 0 | 0 | 0 | 0.5 |
31 | 1 | 5 | 14 | 24 | 0 | 0 | 0 | 0 |
c | - | 2.5 | 15.6 | - | 0 | 0 | 0 | 1.1 |
32 | 3 | 7 | 17 | 21 | 1 | 1 | 3 | 3 |
2.2. Biosensor-Surface Plasmon Resonance Studies (SPR)
Compound | Tel22 (K1; K2) M−1 | cMYC19 (K1; K2) M−1 | AATT (K1) M−1 |
---|---|---|---|
24 | 3.9 × 105; 3.9 × 104 | 3.8 × 106; 1.4 × 105 | <105 |
25 | No Binding | No Binding | No Binding |
26 | 1.3 × 105; 1.7 × 104 | 1.2 × 106; 6.6 × 105 | <105 |
27 | 8.2 × 105; 5.8 × 104 | 5.7 × 105; 4.5 × 104 | <105 |
28 | 8.3 × 105; 6.1 × 104 | 5.0 × 106; 5.6 × 105 | <105 |
29 | 5.9 × 106; 3.9 × 105 | 6.3 × 106; 4.3 × 105 | <105 |
30 | 2.7 × 106; 2.9 × 105 | 8.4 × 106; 3.3 × 105 | <105 |
31 | 5.5 × 106; 4.5 × 105 | 1.2 × 107; 2.7 × 106 | <105 |
32 | 2.1 × 106; 2.2 × 105 | 7.8 × 106; 2.5 × 106 | <105 |
2.3. Circular Dichroism Studies (CD)
2.4. Nuclear Magnetic Resonance Studies (NMR)
2.5. Fluorescence Studies
3. Discussion
4. Experimental
4.1. Synthesis of Cyanines
4.1.1. General Synthesis for the Alkylated Indolenine Salts 15–23 (Scheme 1)
4.1.2. General Synthesis for the Trimethine Cyanine Binding Agents 24–32 (Scheme 1)
4.2. Nucleic Acids
4.3. UV-Thermal Melting
4.4. Biosensor-Surface Plasmon Resonance
4.5. Circular Dichroism
4.6. Fluorescence Titrations
4.7. Nuclear Magnetic Resonance
5. Conclusions
Supplementary Materials
Acknowledgments
Conflicts of Interest
References
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Nanjunda, R.; Owens, E.A.; Mickelson, L.; Dost, T.L.; Stroeva, E.M.; Huynh, H.T.; Germann, M.W.; Henary, M.M.; Wilson, W.D. Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines. Molecules 2013, 18, 13588-13607. https://doi.org/10.3390/molecules181113588
Nanjunda R, Owens EA, Mickelson L, Dost TL, Stroeva EM, Huynh HT, Germann MW, Henary MM, Wilson WD. Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines. Molecules. 2013; 18(11):13588-13607. https://doi.org/10.3390/molecules181113588
Chicago/Turabian StyleNanjunda, Rupesh, Eric A. Owens, Leah Mickelson, Tyler L. Dost, Ekaterina M. Stroeva, Hang T. Huynh, Markus W. Germann, Maged M. Henary, and W. David Wilson. 2013. "Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines" Molecules 18, no. 11: 13588-13607. https://doi.org/10.3390/molecules181113588