DNA duplexes stabilized by modified monomer residues: synthesis and stability

The synthesis of a series of 2'-deoxyuridine analogues modified at the 5-position and a series of 2'-deoxypurines modified at the 8-position is described. Ultraviolet melting studies have been used to assess the stability of DNA duplexes 12- and 8-residues in length that contain these modifications. Of those modified residues which have been incorporated into oligonucleotides, 5-(prop-1-ynyl)-2'-deoxyuridine is found to impart the greatest increase in stability on the DNA duplexes studied. Thermodynamic analyses show that the reason for this increase in stability arises from a decrease in enthalpy which is related to the DNA base stacking process. We suggest that the degree of stabilisation imparted by the propyne moiety may be sequence dependent.