The Influence of Chirality on the β-Amino-Acid Naphthalenediimides/G-Quadruplex DNA Interaction
Abstract
:1. Introduction
2. Results and Discussion
2.1. Naphthalenediimide Design
2.2. G-Quadruplex Topology Analysis
2.3. Circular Dichroism Variable Temperature Studies
2.4. GNINA Modelling
2.5. NDI-DNA Interactions
2.5.1. c-KIT1
2.5.2. h-TELO
2.5.3. TBA
2.5.4. dsDNA
2.6. NDI-DNA Titration Studies
3. Materials and Methods
- c-KIT1: GGG AGG GCG CTG GGA GGA GGG;
- h-TELO: AGG GTT AGG GTT AGG GTT AGG GT;
- TBA: GGT TGG TGT GGT TGG;
- dsDNA: TAT AGC TAT A HEG T ATA GCT ATA.
3.1. Naphthalenediimide Synthesis
General Synthetic Procedure
3.2. Variable-Temperature CD Studies
3.3. Titration Studies
3.4. GNINA Modelling
3.5. HPLC Methodology
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Sequence/Assembly | Average Tm (°C) | ΔTm (°C) 1 |
---|---|---|
c-KIT1 only | 61.2 ± 0.3 | N/A |
1 | 62.1 ± 0.2 | 0.9 |
(S)-2 | 64.4 ± 0.2 | 3.2 |
(R)-3 | 63.4 ± 0.2 | 2.2 |
(S)-3 | 62.7 ± 0.6 | 1.5 |
(R)-4 | 60.3 ± 0.9 | −0.9 |
(S)-4 | 61.6 ± 0.6 | 0.4 |
(R)-5 | 62.9 ± 1.0 | 1.7 |
(S)-5 | 66.6 ± 1.3 | 5.4 |
Sequence/Assembly | Average Tm (°C) | ΔTm (°C) 1 |
---|---|---|
h-TELO only | 63.7 ± 0.8 | N/A |
1 | 64.6 ± 0.4 | 0.9 |
(S)-2 | 65.2 ± 0.7 | 1.5 |
(R)-3 | 64.1 ± 0.5 | 0.4 |
(S)-3 | 63.9 ± 0.2 | 0.2 |
(R)-4 | 64.3 ± 0.4 | 0.5 |
(S)-4 | 65.4 ± 1.7 | 1.7 |
(R)-5 | 64.2 ± 0.5 | 0.4 |
(S)-5 | 66.2 ± 2.0 | 2.4 |
Sequence/Assembly | Average Tm (°C) | ΔTm (°C) 1 |
---|---|---|
TBA only | 50.2 ± 0.4 | N/A |
1 | 51.0 ± 0.1 | 0.8 |
(S)-2 | 50.4 ± 0.1 | 0.2 |
(R)-3 | 50.5 ± 0.2 | 0.3 |
(S)-3 | 50.3 ± 0.1 | 0.1 |
(R)-4 | 50.6 ± 0.3 | 0.4 |
(S)-4 | 50.1 ± 0.1 | −0.1 |
(R)-5 | 50.6 ± 0.2 | 0.4 |
(S)-5 | 50.3 ± 0.1 | 0.1 |
Sequence/Assembly | Average Tm (°C) | ΔTm (°C) 1 |
---|---|---|
dsDNA only | 61.9 ± 1.5 | N/A |
1 | 61.8 ± 0.5 | −0.1 |
(S)-2 | 60.2 ± 0.8 | −1.6 |
(R)-3 | 61.7 ± 1.2 | −0.2 |
(S)-3 | 59.8 ± 0.1 | −2.1 |
(R)-4 | 61.8 ± 0.4 | −0.1 |
(S)-4 | 60.6 ± 0.4 | −1.3 |
(R)-5 | 60.7 ± 1.0 | −1.2 |
(S)-5 | 60.0 ± 1.1 | −1.9 |
Ligand + DNA | KD (μM) | R2 |
---|---|---|
(R)-5 + c-KIT1 | 8.0 ± 2.5 | 0.974 |
(S)-5 + c-KIT1 | 2.6 ± 0.4 | 0.953 |
(R)-4 + h-TELO | 13.6 ± 3.4 | 0.992 |
(S)-4 + h-TELO | 11.0 ± 3.1 | 0.971 |
(R)-5 + dsDNA | 30.7 ± 6.9 | 0.997 |
(S)-5 + dsDNA | 65.2 ± 35.9 | 0.995 |
(R)-4 + dsDNA | 50.2 ± 15.4 | 0.992 |
(S)-4 + dsDNA | 23.6 ± 8.4 | 0.992 |
Sequence Name | Sequence Composition (5′-3′) |
---|---|
c-KIT1 (used experimentally) | GGG AGG GCG CTG GGA GGA GGG |
Amended PDB ID: 3QXR (c-KIT1) | GGG AGG GCG CUG GGA GGA GGG |
h-TELO (used experimentally) | AGG GTT AGG GTT AGG GTT AGG GT |
Amended PDB ID: 6CCW (h-TELO hybrid) | AGG GTT AGG GTT AGG GTT AGG GT |
TBA (used experimentally) | GGT TGG TGT GGT TGG |
PDB ID: 5MJX (TBA) | GGT TGG TGT GGT TGG |
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Clowes, S.R.; Ali, Y.; Astley, O.R.; Răsădean, D.M.; Pantoş, G.D. The Influence of Chirality on the β-Amino-Acid Naphthalenediimides/G-Quadruplex DNA Interaction. Molecules 2023, 28, 7291. https://doi.org/10.3390/molecules28217291
Clowes SR, Ali Y, Astley OR, Răsădean DM, Pantoş GD. The Influence of Chirality on the β-Amino-Acid Naphthalenediimides/G-Quadruplex DNA Interaction. Molecules. 2023; 28(21):7291. https://doi.org/10.3390/molecules28217291
Chicago/Turabian StyleClowes, Samuel R., Yusuf Ali, Olivia R. Astley, Dora M. Răsădean, and G. Dan Pantoş. 2023. "The Influence of Chirality on the β-Amino-Acid Naphthalenediimides/G-Quadruplex DNA Interaction" Molecules 28, no. 21: 7291. https://doi.org/10.3390/molecules28217291