Biomedical subjects

L Kibler-Herzog

Publications and source records attributed to L Kibler-Herzog.

3 recordsLinked to original sources

PubMed1993

Stabilities of duplexes and triplexes of dA19 + dT19 with alternating methylphosphonate and phosphodiester linkages.

Results from UV thermal melting, polyacrylamide gel electrophoresis and circular dichroism (CD) experimetns are used to compare stabilities of complexes formed from 1:1 and 1:2 molar ratio mixtures of dA19 or dA*P19 (alternating phosphodiester and methylphosphonate linkages on the A chain) with dT19 or dT*P19 (alternating phosphodiester and methylphosphonate linkages on the T chain). Complexes formed from 1:1 and 1:2 molar ratio mixtures of dA*P19 with dT19 are more stable than the respective unmodified 'parent' complexes, but less stable than complexes of dA*19 (17 methylphosphonates on the A chain) + dT19. At 0.1 M Na+ complexes containing dT*P19 are less stable than those with dT19, yet more stable than complexes containing the highly modified dT*19 (17 methylphosphonates on the T chain). A value of 2.6 kcal/mol base triplets is calculated for delta H of dA19.2dT19-->dA19.dT19+dT19.

Circular Dichroism↗

PubMed1991

Duplex stabilities of phosphorothioate, methylphosphonate, and RNA analogs of two DNA 14-mers.

The duplex stabilities of various phosphorothioate, methylphosphonate, RNA and 2'-OCH3 RNA analogs of two self-complementary DNA 14-mers are compared. Phosphorothioate and/or methylphosphonate analogs of the two sequences d(TAATTAATTAATTA) [D1] and d(TAGCTAATTAGCTA) [D2] differ in the number, position, or chirality (at the 5' terminal linkage) of the modified phosphates. Phosphorothioate derivatives of D1 are found to be less destabilized when the linkage modified is between adenines rather than between thymines. Surprisingly, no base sequence effect on duplex stabilization is observed for any methylphosphonate derivatives of D1 or D2. Highly modified phosphorothioates or methylphosphonates are less stable than their partially modified counterparts which are less stable than the unmodified parent compounds. The 'normal' (2'-OH) RNA analog of duplex D1 is slightly destabilized, whereas the 2'-OCH3 RNA derivative is significantly stabilized relative to the unmodified DNA. For the D1 sequence, at approximately physiological salt concentration, the order of duplex stability is 2'-OCH3 RNA greater than unmodified DNA greater than 'normal' RNA greater than methylphosphonate DNA greater than phosphorothioate DNA. D2 and the various D2 methylphosphonate analogs investigated all formed hairpin conformations at low salt concentrations.

Base Sequence↗

PubMed1990

Sequence dependent effects in methylphosphonate deoxyribonucleotide double and triple helical complexes.

Deoxyribooligonucleotides containing 19 repeating bases of A, T or U were prepared with normal phosphodiester (dA19, dT19, dU19) or methylphosphonate (dA*19, dT*19, dU*19) linkages. Complexes of these strands have been investigated at 1:1 and 1:2 molar ratios (purine:pyrimidine) by thermal melting and gel electrophoresis. There are dramatic sequence dependent differences in stabilities of complexes containing methylphosphonate strands. Duplexes of dA*19 with dT19 or dU19 have sharp melting curves, increased Tm values, and slopes of Tm versus log (sodium ion activity) plots reduced by about one half relative to their unmodified 'parent' duplexes. Duplexes of dA19 with either dT*19 or dU*19, however, have broader melting curves, reduced Tm values at most salt concentrations and slopes of less than one tenth the values for the unmodified duplexes. Duplex stabilization due to reduced phosphate charge repulsion is offset in the pyrimidine methylphosphonate complexes by steric and other substituent effects. Triple helical complexes with dA19 + 2dT19 and dA19 + 2dU19, which can be detected by biphasic melting curves and gel electrophoresis, are stable at increased Na+ or Mg+2 concentrations. Surprisingly, however, no triple helix forms, even at very high salt concentrations, when any normal strand(s) is replaced by a methylphosphonate strand. Since triple helical complexes with methylphosphonates have been reported for shorter oligomers, inhibition with larger oligomers may vary due to their length and extent of substitution.

Base Sequence↗