The Incorporation of Flexible Hydrophobic Chains Into Double-stranded Dna - the Consequences for Stability

Nucleotide analogues with an aliphatic chain (5C or 10C) attached to C1 of 2- deoxy-D-ribofuranose were synthesized and incorporated into short double helices. The syntheses were accomplished using the reaction of organometallics with alpha-1-chloro-(3, 5-O-diacyl)-1.2-dideoxy-D-ribofuranose. An excellent chemo- and stereoselectivity (inversion at C1) was reached with organocuprates. Duplexes incorporating an aliphatic chain in place of a natural base were more stable (i. e. had a higher T(m)) than those incorporating an abasic site or even a primary amide function attached to C1 by a polymethylenic chain. The increase in T(m) was attributed to a better screening of the aliphatic chain from water in the duplex than in the single-strand oligomer (hydrophobic effect).