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

Diana’s comment on: Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

By Diana Silva Brenes

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Relating molecular structure to function is the first step and one of the greatest challenge to understand nature’s designs or to make novel “functional designs” of our own. This paper by the Chilkoti group begins with statistical analysis of some of the most relevant proteins displaying LCST and UCST behavior. By analyzing the peptide sequences, the authors identify as common motif for both behaviors a high glycine & proline content. Furthermore, for LCST abundance of aromatic residues seems to be a requirement whereas UCST peptides seem to be encoded by a pair of zwitterionic residues.
To test if these observations lead to LCST/UCST phenomena, over 80 model peptides were recombinantly synthesized and their thermoresponsive behavior was measured by UV absorbance while changing the temperature. Each peptide presented the predicted behavior, giving support to their observations. Furthermore, by comparing a few selected examples, they show how an increase in hydrophobicity leads to an increased UCST cloud point and how eliminating one of the residues from azwitterionic pair turns a UCST peptide to an LCST peptide.
The LCST and UCST behavior is, however, a complex phenomenon dependent on protein-protein versus protein-water interactions, which in turn are modulated by more factors aside from the sequence of the protein. The possible scenarios are limitless, and the authors give insight on the most significant: peptide length, concentration, and pH (charge state of protonable atoms).
The robustness of the behavior encoded in the rules they found can be seen by a hybrid peptide containing both an LCST portion and a UCST one. The resulting peptide displays both behaviors, albeit at different temperatures from the “parent” sequences.
Finally, the authors show that searching for the characteristics they determined as important for LCST/UCST behavior throughout the human proteome produces examples of proteins whose function could very well be related to a thermoresponsive behavior, highlighting the applicability of their observations to understand the phenomena that make life as we know it possible.

Quiroz, 2015. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

Updated guidelines for article synopses and blogging

At the end of the GM Schedules page you’ll find the updated guidelines for article synopses and blogging. They are a “work in progress” and I hope we can improve them further by incorporating some of the suggestions discussed recently. Your comments and suggestions regarding this issue will be greatly appreciated.