RNase T1 mimicking artificial ribonuclease.
Recently, artificial ribonucleases (aRNases)--conjugates of oligodeoxyribonucleotides and peptide (LR)(4)-G-amide--were designed and assessed in terms of the activity and specificity of RNA cleavage. The conjugates were shown to cleave RNA at Pyr-A and G-X sequences. Variations of oligonucleotide length and sequence, peptide and linker structure led to the development of conjugates exhibiting G-X cleavage specificity only. The most efficient catalyst is built of nonadeoxyribonucleotide of unique sequence and peptide (LR)(4)-G-NH(2) connected by the linker of three abasic deoxyribonucleotides (conjugate pep-9). Investigation of the cleavage specificity of conjugate pep-9 showed that the compound is the first single-stranded guanine-specific aRNase, which mimics RNase T1. Rate enhancement of RNA cleavage at G-X linkages catalysed by pep-9 is 10(8) compared to non-catalysed reaction, pep-9 cleaves these linkages only 10(5)-fold less efficiently than RNase T1 (k(cat_RNase T1)/k(cat)_(pep)(-9) = 10(5)).
Mironova
N L
NL
Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia.
Pyshnyi
D V
DV
Shtadler
D V
DV
Fedorova
A A
AA
Vlassov
V V
VV
Zenkova
M A
MA
D002412:Cations / Q000737:chemistry; D004722:Endoribonucleases / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D006163:Ribonuclease T1 / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D002412:Cations; D009838:Oligodeoxyribonucleotides; C520008:Pep-9 oligodeoxyribonucleotide-peptide conjugate; D010455:Peptides; D012313:RNA; D004722:Endoribonucleases; D006163:Ribonuclease T1