Artificial ribonucleases: synthesis and RNA cleaving properties of cationic conjugates bearing imidazole residues

Konevetz, D. A.; Beck, Irene E.; Beloglazova, Natalia; Сулименков, И. В.; Silnikov, Vladimir N.; Зенкова, М. А.; Shishkin, G. V.; Vlassov, V. V.

doi:10.1016/s0040-4020(98)01048-5

Cited by 47 publications

(27 citation statements)

References 8 publications

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“…The experimental procedure for the synthesis can be found in Supplementary Information. 1 H and 13 C NMR spectra were consistent with those reported in the literature [29]. 400 MHz): δ = 0.86 (br.t., 6H, CH 3 (CH 2 ) 7 N + ); 1.27-1.34 (m, 22H, CH 3 (CH 2 ) 5 (CH 2 ) 2 N + , + N(CH 2 ) 2 CH 2 (CH 2 ) 2 N + ); 1.70 (m, 4H, CH 3 (CH 2 ) 5 CH 2 CH 2 N + ); 1.82 (m, 4H, + NCH 2 CH 2 CH 2 CH 2 CH 2 N + ); 3.56 (m, 4H, CH 3 (CH 2 ) 6 CH 2 N + ); 3.68 (m, 4H, + NCH 2 (CH 2 ) 3 CH 2 N + ); 3.97-3.99 (m, 24H, + N(CH 2 CH 2 ) 3 N + ).…”

Section: General Procedures Of 1-alkyl-1-azonia-4-azabicyclo[222]octsupporting

confidence: 86%

Synthesis and structure–activity relationship of novel 1,4-diazabicyclo[2.2.2]octane derivatives as potent antimicrobial agents

Yarinich

Буракова

Zakharov

et al. 2015

European Journal of Medicinal Chemistry

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Section: General Procedures Of 1-alkyl-1-azonia-4-azabicyclo[222]octsupporting

confidence: 86%

Synthesis and structure–activity relationship of novel 1,4-diazabicyclo[2.2.2]octane derivatives as potent antimicrobial agents

Yarinich

Буракова

Zakharov

et al. 2015

European Journal of Medicinal Chemistry

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“…Each peptide contained two amino acid residues bearing oppo sitely charged catalytically active groups (the carboxy and amino or guanidinium groups), the distance between them where X are residues of Gly, β Ala, γ aminobutyric acid (GABA), 6 aminohexanoic acid (AHA), or p amino methylbenzoic acid (ABA), respectively. Earlier, 10 we have demonstrated that the efficiency of imidazole containing artificial ribonucleases can be in creased by incorporating 1,4 diazabicyclo[2.2.2]octane (DABCO) derived bis quaternary salts. This can be at tributed to an increase in the affinity of the cationic moi ety of artificial RNase for the negatively charged RNA molecule.…”

Section: Resultsmentioning

confidence: 99%

Artificial ribonucleases 6. Ribonuclease activity of tetrapeptides based on amino acids involved in the catalytic site of RNase T1

et al. 2005

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Tetrapeptides based on amino acids involved in the catalytic site of RNase T1 were synthe sized. These peptides interact with a 96 mer fragment of HIV 1 RNA, which results in phosphodiester bonds splitting. The efficacy of RNA cleavage depends on the mutual arrange ment of oppositely charged amino acids (Glu and Arg or Lys) in a peptide. The introduction of an additional cationic fragment (based on bis quaternary salts of 1,4 diazabicyclooctane) into an RNase mimetic leads to a considerable increase in the efficiency of RNA depolymerization.

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“…18) and compound 2L2; 19 and (2) com pound Dp12 based on two 1,4 diazabicyclo[2.2.2]octane residues, which are connected through a rigid linker and contain oligomethylene fragments at the quaternized 29 and RNase A were used as controls.…”

Section: Oligonucleotides and Rna Cleaving Agentsmentioning

confidence: 99%

Cleavage of RNA bulge loops by artificial RNases

2006

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Sensitivity of phosphodiester bonds in RNA bulge loops to cleavage by short cationic peptides and compounds based on 1,4 diazabicyclo[2.2.2]octane and its conjugates with imid azole was studied. Bulge loops containing from one to seven nucleotides were formed in RNA upon its hybridization with partially complementary oligodeoxyribonucleotides. The efficiency of RNA cleavage depends on the length of a bulge loop, the position of the cleaved phosphodiester bond in the loop, and the nature of the RNA binding fragment of chemical ribonuclease (1,4 diazabicyclo[2.2.2]octane or a cationic peptide). In the absence of Mg 2+ ions, the phosphodiester bond in the CA motif located in the apical position in 4 , 6 , or 7 membered loops is cleaved with the highest efficiency. In the presence of magnesium ions, the selectivity of RNA cleavage within bulge loops is substantially enhanced. In the case of 1,4 diaza bicyclo[2.2.2]octane based compounds, RNA is subjected to cleavage predominantly at the bonds in 4 , 6 , and 7 membered loops, whereas cleavage of other bonds is greatly suppressed.In recent years, numerous low molecular weight com pounds capable of cleaving RNA under physiological con ditions have been designed. 1-4 The RNA cleavage by these compounds occurs predominantly at the regions that are not involved in double stranded structures, such as various loops, single stranded regions, and junctions. The influence of the RNA sequence and secondary struc ture on the efficiency and specificity of cleavage was ex amined only for divalent metal ions. 5-9 The cleavage of phosphodiester bonds located in hairpin loops was stud ied in detail 5-7 since a hairpin is the main structural element of natural RNA and because of important bio logical functions of hairpin loops. 10-12 Among various RNA loops, bulge loops, i.e., RNA regions containing nucleotides that have no complementary bases in the op posite RNA strand are of special interest. These loops arrange the RNA tertiary structure, 13,14 serve as specific RNA protein interaction sites, 15 and form ribozyme ac tive sites. 16 RNA bulge loops are sensitive to cleavage by a wide range of compounds and are potential targets for antisense oligonucleotide based conjugates exhibiting site selective cleavage of RNA. Phosphodiester bonds within RNA bulge loops display a high sensitivity to cleavage by metal ions. 5,8,9 Bonds in most of RNA bulge loops or RNA:DNA complexes are cleaved by divalent metal ions, the bonds located at the 3´ side (in some cases, at the 5´ side) of each nucleotide in the loop being predominantly cleaved. 5In addition, bonds that are adjacent to the bulge loop but are involved in an RNA:DNA duplex were subject to cleavage. 5Earlier, 17 we have studied the sensitivity of phospho diester bonds in one to seven membered RNA bulge loops to cleavage by the 1,4 diazabicyclo[2.2.2]oc tane-histidine conjugate (compound ABL4C3), which cleaves RNA selectively at bonds in 4 and 7 membered loops in the presence of magnesium ions. In the present study, we carried out a comp...

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Artificial ribonucleases: synthesis and RNA cleaving properties of cationic conjugates bearing imidazole residues

Cited by 47 publications

References 8 publications

Synthesis and structure–activity relationship of novel 1,4-diazabicyclo[2.2.2]octane derivatives as potent antimicrobial agents

Synthesis and structure–activity relationship of novel 1,4-diazabicyclo[2.2.2]octane derivatives as potent antimicrobial agents

Artificial ribonucleases 6. Ribonuclease activity of tetrapeptides based on amino acids involved in the catalytic site of RNase T1

Cleavage of RNA bulge loops by artificial RNases

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