Molecules 2013, 18(10), 12751-12767; doi:10.3390/molecules181012751
Article

The Effect of Molecular Crowding on the Stability of Human c-MYC Promoter Sequence I-Motif at Neutral pH

Received: 16 August 2013; in revised form: 26 September 2013 / Accepted: 10 October 2013 / Published: 15 October 2013
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: We have previously shown that c-MYC promoter sequences can form stable i-motifs in acidic solution (pH 4.5–5.5). In terms of drug targeting, the question is whether c-MYC promoter sequence i-motifs will exist in the nucleus at neutral pH. In this work, we have investigated the stability of a mutant c-MYC i-motif in solutions containing a molecular crowding agent. The crowded nuclear environment was modeled by the addition of up to 40% w/w polyethylene glycols having molecular weights up to 12,000 g/mol. CD and DSC were used to establish the presence and stability of c-MYC i-motifs in buffer solutions over the pH range 4 to 7. We have shown that the c-MYC i-motif can exist as a stable structure at pH values as high as 6.7 in crowded solutions. Generic dielectric constant effects, e.g., a shift in the pKa of cytosine by more than 2 units (e.g., 4.8 to 7.0), or the formation of non-specific PEG/DNA complexes appear to contribute insignificantly to i-motif stabilization. Molecular crowding, largely an excluded volume effect of added PEG, having a molecular weight in excess of 1,000 g/mol, appears to be responsible for stabilizing the more compact i-motif over the random coil at higher pH values.
Keywords: i-motif; stability; neutral pH; molecular crowding; excluded volume effect
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MDPI and ACS Style

Cui, J.; Waltman, P.; Le, V.H.; Lewis, E.A. The Effect of Molecular Crowding on the Stability of Human c-MYC Promoter Sequence I-Motif at Neutral pH. Molecules 2013, 18, 12751-12767.

AMA Style

Cui J, Waltman P, Le VH, Lewis EA. The Effect of Molecular Crowding on the Stability of Human c-MYC Promoter Sequence I-Motif at Neutral pH. Molecules. 2013; 18(10):12751-12767.

Chicago/Turabian Style

Cui, Jingjing; Waltman, Phillip; Le, Vu H.; Lewis, Edwin A. 2013. "The Effect of Molecular Crowding on the Stability of Human c-MYC Promoter Sequence I-Motif at Neutral pH." Molecules 18, no. 10: 12751-12767.

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