ISSN:
0020-7608
Keywords:
Computational Chemistry and Molecular Modeling
;
Atomic, Molecular and Optical Physics
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
We have performed a conformational analysis of double-stranded (dA:pT)5 and triple-stranded (dA:pT · pT)5 helices for all possible variants of mutual orientation of oligoamide and oligonucleotide strands by means of AMBER 3.0. Computation results showed that the conformational flexibility of chimeric helices is practically like the DNA flexibility, although orientation of atoms around the amide bond is almost planar. cis- and trans-orientations are close in energy. Permissible changes in helical parameters of chimeric helices practically coincide with the corresponding parameters of double- and triple-stranded DNA helices. Double-stranded chimeric helices exhibit a tendency to twist accompanied by helical pitch decreasing. Three-stranded chimeric complexes, on the contrary, exhibit a tendency to unwinding. Energy gain of chimeric helices is noticeable. Thus, double-stranded chimeras are characterized by the energy of 20 kcal/mol per monomer unit lower than double-stranded DNAs. The energy gain of triple-stranded chimeric complexes is about 40 kcal/mol per monomer unit. There is qualitative correlation between the experimentally obtained enthalpy of chimeric complexes and their calculated potential energy. It fully explained the ability of oligoamides to interact with DNA following oligoamide strand invasion of the duplex through D-loop formation. The dependence of energy on mutual strand orientation in chimeric duplexes is weak. Energy penalty of duplexes with parallel orientation of 5′ → 3′ and N → C chain vectors is about 0,7 kcal/mol per monomer unit. The dependence of energy on mutual strand orientation in chimeric triplexes is much more appreciable. The most advantageous is parallel orientation of 5′ → 3′ and N → C vectors of Watson-Crick chains accompanied by antiparallel orientation of the Hoogsteen oligoamide chain. It was shown that the stability of double-stranded oligonucleotides may be increased as a result of oligoamide insert of three or four monomer units in one of the oligonucleotide chains. The length and base sequence in the insert allowed one to modulate the degree of duplex stabilization. It is important that such stabilization may be obtained without any distortion in vector character of nucleotide duplex formation. It is evident that this method of stabilization of helices is suitable also for triplexes. Moreover, in this way, one can overcome the difficulties connected with the low penetration ability of PNA in living cells. © 1994 John Wiley & Sons, Inc.
Additional Material:
8 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/qua.560520712
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