RNA-Cleaving Oligonucleotide-Peptide Conjugates

Миронова, Н. Л.; Pyshnyi, D. V.; Иванова, Е. М.

doi:10.1007/978-3-642-18510-6_10

Cited by 4 publications

(7 citation statements)

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“…In addition, the POCs described here do 64 HIV-1 gagRNA; 13 Human c-raf-1 mRNA; 28 tRNA Lys . 7 Peptidyl−oligonucleotide conjugates have been shown to induce efficient cleavage of RNA sequences leading to irreversible damage of biologically significant RNA targets. At one extreme, direct site-specific cleavage without significant catalytic amplification was observed for complementary RNA targets (demonstrated in this research).…”

Section: ■ Conclusionmentioning

confidence: 99%

Peptidyl–Oligonucleotide Conjugates Demonstrate Efficient Cleavage of RNA in a Sequence-Specific Manner

et al. 2015

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Described here is a new class of peptidyl-oligonucleotide conjugates (POCs) which show efficient cleavage of a target RNA in a sequence-specific manner. Through phosphoramidate attachment of a 17-mer TΨC-targeting oligonucleotide to amphiphilic peptide sequences containing leucine, arginine, and glycine, zero-linker conjugates are created which exhibit targeted phosphodiester cleavage under physiological conditions. tRNA(Phe) from brewer's yeast was used as a model target sequence in order to probe different structural variants of POCs in terms of selective TΨC-arm directed cleavage. Almost quantitative (97-100%) sequence-specific tRNA cleavage is observed for several POCs over a 24 h period with a reaction half-life of less than 1 h. Nontargeted cleavage of tRNA(Phe) or HIV-1 RNA is absent. Structure-activity relationships reveal that removal of the peptide's central glycine residue significantly decreases tRNA cleavage activity; however, this can be entirely restored through replacement of the peptide's C-terminal carboxylic acid group with the carboxamide functionality. Truncation of the catalytic peptide also has a detrimental effect on POC activity. Based on the encouraging results presented, POCs could be further developed with the aim of creating useful tools for molecular biology or novel therapeutics targeting specific messenger, miRNA, and genomic viral RNA sequences.

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Section: ■ Conclusionmentioning

confidence: 99%

Peptidyl–Oligonucleotide Conjugates Demonstrate Efficient Cleavage of RNA in a Sequence-Specific Manner

et al. 2015

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“…[7,8,14] The tetrathymidylate conjugate was one of the most active among the compounds. [7,8,14] The tetrathymidylate conjugate was one of the most active among the compounds.…”

Section: Resultsmentioning

confidence: 99%

Ribonuclease Activity of the Peptides with Alternating Arginine and Leucine Residues Conjugated to Tetrathymidilate

Миронова¹,

Boutorine²,

Pyshnyi³

et al. 2004

Nucleosides, Nucleotides and Nucleic Acids

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RNA cleaving conjugates have been prepared by attachment of oligodeoxyribonucleotide TTTT to peptides containing arginine, leucine, proline and serine residues. The highest activity was displayed by the conjugates containing peptides with alternating arginine and leucine residues (LR)4G-amide. Ribonuclease activity of the conjugates pep-T4 decreases in the order T4-(LR)4G > T4-(LR)2G > T4-(LLRR)2G > T4-(LR)2PRLRG > S2R3-Hmda-T4 > or = R5 double dagger (LR)3. According to CD spectra, the free peptide (LR)4G-amide in water solution at neutral pH and physiological ionic strength has no pronounced secondary structure whereas conjugated to oligonucleotide it acquires a folding similar to alpha-helix.

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“…In addition, metal complexes of chelating copper ions and various lanthanides , also possess RNAase activity. Similarly, a number of synthetic polypeptides have been shown to display RNA cleaving activity, with good efficiency and specificity . The RNAase activity of polypeptides depends on the nature of the amino acids present in them.…”

Section: 3 Artificial Enzymesmentioning

confidence: 99%

“…Mironova and co-workers have synthesized a series of POCs capable of cleaving RNAs in a sequence specific manner. − The oligonucleotides 171 , 172 , and 173 with different specificities were linked to the core (catalytic) peptide sequence, [Arg-Leu] 4 -Gly, using the SPFC method to obtain the conjugate shown in Figure . The oligonucleotide and peptide fragments of these conjugates (pep− 171 , pep− 172 , and pep− 173 in Figure ) were connected by N -alkylphosphoramidate linkages between the 5‘-terminal phosphate of the oligonucleotide and the N-terminal-α-amino group of the corresponding oligopeptide.…”

Section: 3 Artificial Enzymesmentioning

confidence: 99%

“…Similarly, a number of synthetic polypeptides have been shown to display RNA cleaving activity, with good efficiency and specificity. 248 The RNAase activity of polypeptides depends on the nature of the amino acids present in them. Short oligopeptides with alternating hydrophobic and basic amino acids displayed negligible RNAase activity, but conjugation of these peptides to ODNs is shown to improve their RNAase activity dramatically but not their DNAase activity.…”

Section: Artificial Enzymesmentioning

confidence: 99%

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