NUCLEIC-ACID ANALOGS WITH RESTRICTED CONFORMATIONAL FLEXIBILITY IN THE SUGAR-PHOSPHATE BACKBONE (BICYCLO-DNA) .3. SYNTHESIS, PAIRING PROPERTIES, AND CALORIMETRIC DETERMINATION OF DUPLEX AND TRIPLEX STABILITY OF DECANUCLEOTIDES FROM 2'-DEOXY-3',5'-ETHANO-BETA-D-RIBOFURANOSYL]ADENINE AND THYMINE
M. Tarkoy et al., NUCLEIC-ACID ANALOGS WITH RESTRICTED CONFORMATIONAL FLEXIBILITY IN THE SUGAR-PHOSPHATE BACKBONE (BICYCLO-DNA) .3. SYNTHESIS, PAIRING PROPERTIES, AND CALORIMETRIC DETERMINATION OF DUPLEX AND TRIPLEX STABILITY OF DECANUCLEOTIDES FROM 2'-DEOXY-3',5'-ETHANO-BETA-D-RIBOFURANOSYL]ADENINE AND THYMINE, Helvetica Chimica Acta, 77(3), 1994, pp. 716-744
The synthesis of a new type of oligonucleotide ('bicyclooligodeoxynucl
eotide' = bcd(X(n))) displaying less conformational flexibility in its
sugar-phosphate backbone is described, and a characterization of the
pairing properties and energetics of the decamers bcd(T-10) and bcd(A(
10)) with each other and with complementary RNA and DNA sequences by U
V-spectroscopic and calorimetric techniques is given. The results can
be summarized as follows: i) bcd(T-10) pairs less strongly to compleme
ntary RNA and DNA, whereas bcd(A(10)) Forms stronger duplexes relative
to the natural system. ii) bcd(A(10)) discriminates between a complem
entary oligodeoxynucleotide with a mismatch in the center in the same
way as d(A(10)), indicating equal base-pairing selectivity. iii) bcd(A
(10)) forms more stable triplexes with d(T-10) of the pyrimidine-purin
e-pyrimidine (py.pu.py) motif than d(A(10)). iv) The stability of dupl
exes containing a bicyclic strand is more sensitive towards salt conce
ntration. The higher sensitivity in bcd(A(10)) containing duplexes is
due to a higher differential cation uptake. v) Differential scanning c
alorimetric (DSC) analysis of duplex-formation enthalpies shows Delta
H-upsilon H duplexes containing bicyclooligonucleotides to be more neg
ative than Delta H?(cal, which is compatible with the formation of cat
enated structures, vi) Isothermal titration calorimetry (ITC) provides
a complete set of thermodynamic data including duplex and tripler ass
ociation constants for the systems d(A(10))/d(T-10), bcd(A(10))/d(T-10
), d(A(10))/bcd(T-10), bcd(A(10))/bcd(T-10). vii) All duplexes contain
ing bicyclic strands show a (numerically) reduced paining entropy term
with respect to that of the natural system. viii) Enthalpies from DSC
and ITC are similar, suggesting that the enthalpic contribution from
ordered single strands to the overall duplex-formation enthalpy plays
a minor role in the duplexes investigated.