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7‐ Deazaadenosine : Oligoribonucleotide building block synthesis and autocatalytic hydrolysis of base‐modified hammerhead ribozymes
Author(s) -
Seela Frank,
Mersmann Karin,
Grasby Jane A.,
Gait Michael J.
Publication year - 1993
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19930760502
Subject(s) - chemistry , ribozyme , autocatalysis , residue (chemistry) , hydrolysis , stereochemistry , ribonucleotide , catalysis , substrate (aquarium) , nucleic acid , phosphonate , nucleotide , biochemistry , rna , gene , oceanography , geology
Abstract A 7‐deazaadenosine ( = tubercidin; c 7 A; 1 ) building block for solid‐phase oligoribonucleotide synthesis was prepared. The amino group of 1 was protected with the (dimethylamino)methylidene residue (→ 3 ), and the monomethoxytrityl group was introduced at OHC(5′) (→ 4 ). Protection of OHC(2′) was carried out by silylation, showing that use of the (i‐Pr) 3 Si group resulted in high 2′‐ O ‐selectivity (→ 5b , 80%). Reaction of 5b with PCl 3 afforded the phosphonate 7 which was used in solid‐phase oligoribonucleotide synthesis. The autocatalytic hydrolysis of hammerhead ribozymes using pG‐G‐G‐A‐G‐U‐C‐A‐G‐U‐C‐C‐C‐U‐U‐C‐G‐G‐G‐G‐A‐C‐U‐C‐U‐G‐A‐A‐G‐A‐G‐G‐C‐G‐C as substrate strand (S) and modified G‐C‐G‐C‐C‐G‐A‐A‐A‐C‐U‐C‐C‐C as enzyme strand (E) was studied. When c 7 A replaced A 13 or A 14 , a small decrease of catalytic activity was observed, while modification in position A 15 enhanced the autocatalytic hydrolysis. The results demonstrate, that the atom N(7) of adenosine in any of these positions is not crucial for ribozyme action.