The chemical behavior of sulfur-containing oligonucleotides and their react
ivity in self-assembled nucleic acids (NA) and specific NA-protein complexe
s is considered. Reviewed are postsynthetic approaches that allow introduci
ng sulfur-containing linkages at preselected positions of the sugar-phospha
te backbone of DNA and between neighboring nucleobases, to incorporate disu
lfide bridges between complementary strands of double- and triple-stranded
DNAs, in large catalytic RNA, etc. Special reference is given to the site-s
pecific chemical modifications as a tool for elucidating the structure, fol
ding, and function of biomolecules. Structure-directed chemical reactions a
re shown to be helpful in detecting point mutations in DNA, targeting the m
odifications on specific positions of NA, probing the molecular recognition
in protein-DNA interfaces, studying the conformational dynamics of nucleic
acids, and discriminating between different folding models.