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From Phosphate to Bis(methylene) Sulfone: Non‐Ionic Backbone Linkers in DNA
Author(s) -
Hutter Daniel,
Blaettler Monika O.,
Benner Steven A.
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200209)85:9<2777::aid-hlca2777>3.0.co;2-1
Subject(s) - chemistry , methylene , phosphinate , dna , stereochemistry , sulfone , phosphonate , duplex (building) , crystallography , polymer chemistry , medicinal chemistry , organic chemistry , biochemistry , fire retardant
Chimeric DNA molecules containing four different linking groups, the natural phosphate, 5′‐methylenephosphonate, bis(methylene)phosphinate, and bis(methylene) sulfone (see Fig. 1 ), were directly compared for their ability to form duplexes with complementary DNA and DNA chimeras. From melting temperatures for analogous complementary sequences, general conclusions about the impact of geometric distortion of the internucleotide linkage around the two POC bridges were drawn, as were conclusions about the impact on duplex stability that arises from the removal of the negative charge in the linking group. Each structural perturbation diminished the melting temperature, by ca. −2.5° per modification for the 5′‐methylenephosphonate, −3.5° per modification for the bis(methylene)phosphinate, and −4.5° per modification for the bis(methylene) sulfone linker. These results have implications for DNA chemistry including the design of ‘antisense' candidates and the proposal of alternative genetic materials in the search for non‐terrean life.