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Hexamer oligonucleotide topology and assembly under solution phase NMR and theoretical modeling scrutiny
Author(s) -
Evstigneev Maxim P.,
Parkinson John A.,
Lantushenko Anastasia O.,
Kostjukov Viktor V.,
Pahomov Valery I.
Publication year - 2010
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.21515
Subject(s) - random hexamer , chemistry , monomer , crystallography , nuclear magnetic resonance spectroscopy , topology (electrical circuits) , spin diffusion , duplex (building) , oligonucleotide , diffusion , thermodynamics , stereochemistry , polymer , dna , combinatorics , organic chemistry , physics , mathematics , biochemistry
The entire family of noncomplementary hexamer oligodeoxyribonucleotides d(GCXYGC) (X and Y = A, G, C, or T) were assessed for topological indicators and equilibrium thermodynamics using a priori molecular modeling and solution phase NMR spectroscopy. Feasible modeled hairpin structures formed a basis from which solution structure and equilibria for each oligonucleotide were considered. 1 H and 31 P variable temperature‐dependent (VT) and concentration‐dependent NMR data, NMR signal assignments, and diffusion parameters led to d(GCGAGC) and d(GCGGGC) being understood as exceptions within the family in terms of self‐association and topological character. A mean diffusion coefficient D 298 K = (2.0 ± 0.07) × 10 −10 m 2 s −1 was evaluated across all hexamers except for d(GCGAGC) ( D 298 K = 1.7 × 10 −10 m 2 s −1 ) and d(GCGGGC) (D 298 K = 1.2 × 10 −10 m 2 s −1 ). Melting under VT analysis (T m = 323 K) combined with supporting NMR evidence confirmed d(GCGAGC) as the shortest tandem sheared GA mismatched duplex. Diffusion measurements were used to conclude that d(GCGGGC) preferentially exists as the shortest stable quadruplex structure. Thermodynamic analysis of all data led to the assertion that, with the exception of XY = GA and GG, the remaining noncomplementary oligonucleotides adopt equilibria between monomer and duplex, contributed largely by monomer random‐coil forms. Contrastingly, d(GCGAGC) showed preference for tandem sheared GA mismatch duplex formation with an association constant K = 3.9 × 10 5 M −1 . No direct evidence was acquired for hairpin formation in any instance although its potential existence is considered possible for d(GCGAGC) on the basis of molecular modeling studies. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 1023–1038, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com