THE INCORPORATION OF FLEXIBLE HYDROPHOBIC CHAINS INTO DOUBLE-STRANDEDDNA - THE CONSEQUENCES FOR STABILITY

Nucleotide analogues with an aliphatic chain (5C or 10C) attached to C 1 of 2- deoxy-D-ribofuranose were synthesized and incorporated into sh ort 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 aliphat ic chain in place of a natural base were more stable (i. e. had a high er T(m)) than those incorporating an abasic site or even a primary ami de 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 ef fect).