Kiara’s comment on: A 2,7-diamino-1,4,8-triazanaphthalene derivative selectively binds to cytosine bulge DNA only at a weakly acidic pH

By Kiara N. Villa Del Valle

KNV blog image 18-05

This paper focuses reports how through a change in the pH, their compound gets protonated and through hydrogen bonds, the compound and the base binds. Lastly, the better-known DNA structure the double helix, but there are other varieties such as hairpin loops, interior loops, multi-branched loops and bulge loops. Bulge loops, are when an extra base winds up on one side of the DNA strand. This can happen when the helix missing a base or an extra one was inserted during the DNA copying process. This anomaly can cause cancer or triplet diseases. They first performed experiments to determine the pH dependence if the azaDANP. They changed the pH from 1.0 to 9.0 and it shows a hypochromic and hypsochromic shifts as the pH was changing. They also plotted the absorption in terms of the pH and determined a pKaH (pKa of the protonated form) of 4.3, a lower pKaH of 6.8 for a previously described compound. This decrease was due to the decreased basicity of the ring nitrogen by the substitution at C4-N. To get information about the azaDANP binding to the C-bulge, they simulated possible complexes between azaDANP and cytosine, it showed that the protonation likely occurs at N1 for the complex formation. They performed more experiments to measure the absorption spectra of azaDANP in presence of T, G, A and C bulged DNA, at pH 7.0 and 5.5 at room temperature. We want to focus in this, at 5.5 pH there is a new absorption band at 407 nm that in neutral pH is not observed and therefore suggesting that the formation is pH sensitive. The thermal stability of the azaDANP-C-bulge was investigated with absorption with variable temperature. We can see that the peak observed at 407 nm at 2 °C decreases as the temperature is increased to 80 °C. This shows the equilibrium of azaDANP and GCG/CC DNA to form a binary complex and, therefore, appearing to be temperature dependent.

 


Aikawa, 2017. A 2,7-diamino-1,4,8-triazanaphthalene derivative selectively binds to cytosine bulge DNA only at a weakly acidic pH

7 thoughts on “Kiara’s comment on: A 2,7-diamino-1,4,8-triazanaphthalene derivative selectively binds to cytosine bulge DNA only at a weakly acidic pH

  1. Rating (synopsis): 0/5
    Rating (figure): 1/5

    This synopsis is so confusing that in order to understand it, I had to revisit the paper. Although it is partially due to difficulties with the language, it also seems to reflect a lack of grasping the meaning of the paper and the experiment. It fails to convey the purpose of the research, to explain the importance of controlling the pKa of the reported compound, it does not even attempt to explain where azaDANP comes from, it mentions UV experiments between the presented compound without saying anything about the results. Some parts lack information to the point where the results seem to be miss-interpreted: e.g. the fact that absorbance at 407 nm decreases with increasing temperature does not in itself mean that it is a binary complex. Furthermore, talking about “C4-N” or “N1 for the complex formation” is impossible to understand for the reader without more information.
    I’m aware that this is very hard criticisms considering that this is the first presentation ever by a recent undergraduate student. My advice would be that in order to take more advantage of the learning opportunity of a lab, she should prepare these writings working closely with her graduate mentor or ask for help from other willing grad students at the lab. I’ve seen Kiara’s hard work and truly believe in her potential.
    The figure has the structure of azaDANP, which is important to understand the synopsis, but other than that, conveys very little information.

  2. Rating (synopsis): 1/5
    Rating (figure): 1/5

    Kiara’s narrative does not have great readability but I like the attempt of explaining the importance of the C-bulge, which was unknown to me before I read the article. It is important, in the synopsis, to establish the C-bulge as one of the main actors in the article to capture the attention of the reader. Nevertheless, the synopsis needs some fine-tuning.

    The images that we generate for the articles are supposed to be, for the most part, self-explanatory. Kiara’s image does not explain much of the article but rather generated questions. For example, what are those absorbance graphs trying to say? why do you measure at pH 1 and 9? I am sure Kiara, and everybody, will get better at this. After all, for some of us, it’s the first time in this type of exercise.

  3. Rating (synopsis): 2/5
    Rating (figure): 3/5

    The summary has certain information gaps that I believe are important to understand the article. For a next occasion it should focus on what they did, how they did it and what were the most relevant results for a better explanation of the information presented in the article.

    Although the image does have something to do with what is being talked about in the article, it does not correlate with what is mentioned in the summary. It should be modified and focus more for example on the importance of Pka in the experiment.

  4. Rating (synopsis): 1/5
    Rating (figure): 0/5

    While the paper itself is a very interesting, informative and even didactic for a probe, Kiara’s comment seems unorganized. She clearly wants to spill all the data to give an idea of what the paper is about, but as a reader, you never see that. So, I understand why would one write in this manner. As we follow her post, it was not clear why this probe was even developed in the first place. You are left to deduce by yourself by all the given information. If this was clearer by her comment it would be easier to follow the rest of the information. When writing these summaries, as we do with abstract, we first give context to the reader connecting each dot, no rational left behind. In the case of these blog post, we want to convey the rational, not necessarily show off the data, unless necessary to finish the story. As the image goes, I do not understand it. I could infer that by somehow replacing C with zaDANP absorbance changes somehow. And as we know, that is not the message.

  5. Rating (synopsis): 3/5
    Rating (figure): 3/5

    In the beginning, while reading the synopsis, I got a little confused when she uses the transition word ”Lastly” in the second sentence. But overall, the introduction in the synopsis was good and how she explains the C-bulge. In the figure, maybe using arrows or other types of figures would have been better to understand the meaning of it. For example, making it more clear that ”upon binding of azaDANP to the cytosine bulge DNA, a new absorption band at 407 nm appears” which corresponds to the second graph shown on the TOC.

  6. Rating (Synopsis): 2/5
    Rating (Figure): 1/5

    Kiara’s synopsis has several grammatical errors that make it hard-to-read, like omissions of the to-be verb in various occasions, but those are minor compared to the lack of a coherent flow throughout the whole synopsis. For example, she begins with a description of what the article’s actually about and continues talking about the importance of the C-bulge, but then goes on talking about experiments that determine the pH dependence of the azaDANP without even mentioning what the azaDNP is, its relation to the introduction that was just presented, and why it needs to be pH dependent. I believe that Kiara tried to provide us with a good synopsis, but she needed to ask someone (preferably hers or any other willing and available grad student) to help her understand the science and proofread the synopsis.

    Regarding the figure, I don’t think it conveys the idea behind the article as it doesn’t have a coherent flow and has poor placing of the different images that compose it.

  7. Rating (Synopsis): 2/5
    Rating (Figure): 3/5

    As I started reading the synopsis, I got confused several times. Even though I had a relatively difficult time going through it, I understood most of what you tried to explain. In my opinion it would have been a smoother read if you arranged the ideas better. Regarding your figure, I think it would have been good if you used a more detailed imagery including the process of the protonation, followed by binding. This, accompanied with the graphs, would work as a easier to read map with evidence attached.

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