ACCELERATION OF THE ZN2-PROMOTED PHOSPHODIESTER HYDROLYSIS OF OLIGONUCLEOTIDES BY THE 3'-TERMINAL MONOPHOSPHATE GROUP - INTRASTRAND PARTICIPATION OVER SEVERAL NUCLEOSIDE UNITS()

The Zn2+-promoted hydrolysis of the 5'-terminal ribonucleoside phospho diester bond in chimeric ribo/deoxyribo oligonucleotide 3'-monophospha tes, Up(Tp)(4) and Up(Tp),, and their dephosphorylated analogue, Up(Tp )(3)T, has been studied at various metal ion and substrate concentrati ons, and in the presence and absence of deoxyribooligonucleotide 3'-mo riophosphates, (Tp)(n), containing no cleavable ribonucleoside phospho diester bond, The results strongly suggest that the rate-accelerating effect of the 3'-terminal monophosphate group on the phosphodiester hy drolysis is of intramolecular origin: the Zn2+ ion bridges the favoure d site of coordination, i.e. the terminal monophosphate group,and the cleaving phosphodiester bond. The 3'-monophosphate group also causes t he reaction order in [Zn2+] to deviate from unity, the values obtained with Up(Tp)(3)T, Up(Tp)(4) and Up(Tp)(9) being 1.1, 1.4 and 1.7, resp ectively. Possibly, the intramolecular participation of the 3'-monopho sphate bound Zn2+ ion is facilitated by another Zn2+ ion that stabiliz es the folded conformation of the oligonucleotide chain in the reactiv e Zn2+/substrate macrochelate.