Transesterification phosphodiesters

HPNPP (101) was also used to probe the catalytic ability of zinc- and copper-containing calix[4]arenes that carried two or three [12]ane-N3 macrocycles on their upper rim. Cooperativity was found between the catalytically active metal complexes during phosphodiester transesterification provided that they were adjacent to each other, i.e. on proximal positions of the calixarene rim, whereas those on opposite... 

Scheme 14-1. General in-line monoanionic mechanism of phosphodiester cleavage transesterification catalyzed by hairpin ribozyme the first proton transfer (PT1), the nucleophilic attack (Nu), and the exocyclic cleavage (Cl) steps are shown, and the Oip and O2p pathways are indicated by blue and red colored hydrogens, respectively. For the uncatalyzed model reaction in solution, the Ojp and O2p pathways are energetically equivalent...

Ibe principle found for zinc(II) was applied to ) complex models by Young et al. (25). The hydroxyl function of copper complex 27a deprotonates with a p value of 8.8 to yield 27b, which cleaves phosphodiester bis(2,4-dinitrophenyl) phosphate (BDP ) by transesterification to produce 28 ( (BDP ) = 7.2 x -1 M-1sec-1 at 25°C see Scheme 5). The analogous complex with a hydroxyethyl pendent cleaves the diester predominantly by hydrolysis, which suggests that the reactive species is not Cun-alkoxide, but —OH-. The rate A(BDP") of... 

The study of posttranscriptional processing of RNA molecules led to one of the most exciting discoveries in modern biochemistry—the existence of RNA enzymes. The best-characterized ribozymes are the self-splicing group I introns, RNase P, and the hammerhead ribozyme (discussed below). Most of the activities of these ribozymes are based on two fundamental reactions transesterification (Fig. 26-13) and phosphodiester bond hydrolysis (cleavage). The substrate for ribozymes is often an RNA molecule, and it may even be part of the ribozyme itself. When its substrate is RNA, an RNA cat-... 

The mechanism of self-splicing in this case is somewhat different from that observed in the spliceosome reaction (fig. 28.21). First the 3 hydroxyl group of the guanosine cofactor attacks the phosphodiester bond at the 5 splice site. This is followed by another transesterification reaction in which the 3 hydroxyl group of the upstream RNA attacks the phosphodiester bond at the 3 splice site, thereby completing the splicing reaction. The final reaction products include the spliced rRNA and the excised oligonucleotide. 

The hydrolysis of adenosine 3. 5 -cyclic monophosphate (cAMP) by the cobalt complexes (215) was considered here earlier,187 as was the Ce(IV)-catalysed hydrolysis of phospho monoesters in nucleotides.189 A review (ca 100 references) on current data on the mechanism of cleavage-transesterification of RNA has appeared.258 In this review special attention was focused on the two crucial steps in the hydrolysis of RNA, i.e. cleavage-transesterification and hydrolysis of the cyclic phosphodiester (Scheme 14). The catalysis of various amines for the hydrolysis of RNA has been looked at and ethylenediamine and propane-1,3-diamine are highly active under physiological conditions because they exist as the catalytically active monocation forms.259... 

The so-called ribozymes (Box 22) were discovered in 1982 by T. Cech and S. Altman. The naturally occurring species catalyze predominantly one reaction type -hydrolysis or transesterification of phosphodiester bonds in RNA. A very important natural ribozyme is the ribosome. On the basis of X-ray crystallographic investigations it was recently shown that the active site for the peptide bond-formation reaction is composed exclusively of RNA. 

Guanidines have been implemented early as recognition elements, guided by the apparent function of arginine in protein structures. The C2-symmetric, chiral anion receptor 52 was introduced by Lehn, Schmidtchen and de Mendoza consecutively and studied in various modifications (Scheme 13) [23c]. For example, an elaborate system based on 52 provided reasonable enantioselective recognition of amino acids [23c, 28]. Furthermore, bis(guanidinium) compounds catalyze RNA hydrolysis in the presence of external base via phosphodiester complexation [29]. The,se functional elements were joined in receptor 53 to yield a functional transesterification catalyst [30]. 

Cleavage of nucleic acids refers to a reaction that results in the breakage of bonds in the phosphodiester backbone of a polynucleotide chain. There are two types of reactions resulting in the cleavage of either P-O or C-O bonds in the nucleic acid backboue (see Figure Id). Cleavage of the P-O bond occurs as a result of uucleophilic attack ou the phosphorus atom via either an intermolecular reaction with a H2O molecule hydrolysis) or an intramolecular reactiou involving the ribose 2 -OH transesterification). Of these two reactions, transesterification is specific to RNA (since DNA lacks a 2 -OH moiety) and can be catalyzed by many M- +... 

The 3 -OH terminus of exon 1 then attacks the phosphodiester bond between the intron and exon 2. Exons 1 and 2 become joined, and the intron is released in lariat form. Again, this reaction is a transesterilication. Splicing is thus accomplished by two transesterification reactions rather than by hydrolysis followed by ligation. The first reaction... 

One possibility is that the 3 end of the poly(U) donor strand cleaves the phosphodiester bond on the 5 side of the insertion site. The newly formed 3 terminus of the acceptor strand then cleaves the poly(U) strand on the 5 side of the nucleotide that initiated the attack. In other words, a uridine residue could be added by two transesterification reactions. This postulated mechanism is similar to the one in RNA splicing. 

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