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Folding thermodynamics of the hybrid‐1 type intramolecular human telomeric G‐quadruplex
Author(s) -
Shek Yuen Lai,
Noudeh Golamreza Dehghan,
Nazari Mozhgan,
Heerklotz Heiko,
AbuGhazalah Rashid M.,
Dubins David N.,
Chalikian Tigran V.
Publication year - 2014
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22317
Subject(s) - g quadruplex , chemistry , folding (dsp implementation) , intramolecular force , molecule , sequence (biology) , guanine , molecular dynamics , dna , crystallography , stereochemistry , computational chemistry , biochemistry , organic chemistry , gene , engineering , nucleotide , electrical engineering
Guanine‐rich DNA sequences that may form G‐quadruplexes are located in strategic DNA loci with the ability to regulate biological events. G‐quadruplexes have been under intensive scrutiny owing to their potential to serve as novel drug targets in emerging anticancer strategies. Thermodynamic characterization of G‐quadruplexes is an important and necessary step in developing predictive algorithms for evaluating the conformational preferences of G‐rich sequences in the presence or the absence of their complementary C‐rich strands. We use a combination of spectroscopic, calorimetric, and volumetric techniques to characterize the folding/unfolding transitions of the 26‐meric human telomeric sequence d[A 3 G 3 (T 2 AG 3 ) 3 A 2 ]. In the presence of K + ions, the latter adopts the hybrid‐1 G‐quadruplex conformation, a tightly packed structure with an unusually small number of solvent‐exposed atomic groups. The K + ‐induced folding of the G‐quadruplex at room temperature is a slow process that involves significant accumulation of an intermediate at the early stages of the transition. The G‐quadruplex state of the oligomeric sequence is characterized by a larger volume and compressibility and a smaller expansibility than the coil state. These results are in qualitative agreement with each other all suggesting significant dehydration to accompany the G‐quadruplex formation. Based on our volume data, 432 ± 19 water molecules become released to the bulk upon the G‐quadruplex formation. This large number is consistent with a picture in which DNA dehydration is not limited to water molecules in direct contact with the regions that become buried but involves a general decrease in solute–solvent interactions all over the surface of the folded structure. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 216–227, 2014.