ACCELERATION OF THE ZN2-PROMOTED PHOSPHODIESTER HYDROLYSIS OF OLIGONUCLEOTIDES BY THE 3'-TERMINAL MONOPHOSPHATE GROUP - INTRASTRAND PARTICIPATION OVER SEVERAL NUCLEOSIDE UNITS()
S. Kuusela et al., ACCELERATION OF THE ZN2-PROMOTED PHOSPHODIESTER HYDROLYSIS OF OLIGONUCLEOTIDES BY THE 3'-TERMINAL MONOPHOSPHATE GROUP - INTRASTRAND PARTICIPATION OVER SEVERAL NUCLEOSIDE UNITS(), Perkin transactions. 2, (9), 1996, pp. 1895-1899
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.