RNase T1 mimicking artificial ribonuclease

Recently, artificial ribonucleases (aRNases)—con-jugates of oligodeoxyribonucleotides and peptide (LR)4-G-amide—were designed and assessed in terms of the activity and specificity of RNA clea-vage. The conjugates were shown to cleave RNA at Pyr-A and G–X sequences. Variations of oligonu-cleotide 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 nonadeoxyribonucleo-tide of unique sequence and peptide (LR)4-G-NH2 connected by the linker of three abasic deoxyribo-nucleotides (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 108 compared to non-catalysed reaction, pep-9 cleaves these linkages only 105-fold less efficiently than RNase T1 (kcat_RNase T1/kcat_pep-9 105)