Nucleopeptides

To investigate the competition between the sulfur atom and the highly reactive GpG sequence we extended this study and used the nucleopeptide model Met-d(TpGpG)-2. Cisplatin is well known to preferentially bind to the N(7) atoms of two neighboring guanines in DNA [81],... 

Synthesis of Oligonucleotide-Peptide Conjugates and Nucleopeptides. Eritja, R. In Solid Phase Synthesis Kates, S. A., Albericio, F., Eds. Dekker New York, 2000, pp 529-548. 

Even under weakly basic conditions (pH >9) the entire fatty acid, carbohydrate, nucleotide, and phosphate parts can be cleaved from these compounds. While under acidic conditions an attack on the N- or O-glycosidic bonds in nucleopeptides and glycopeptides may occur, resulting in anomerization and even a complete deglycosidation. 

PGA-mediated selective deprotection of the phenylacetyl-protected nucleobase has been implemented successfully in the synthesis of nucleopeptides (Scheme... 

Proteases, such as thermitase,papain,f " l and subtilisinf have been employed for the deprotection of tert-butyl and methyl esters from various glycopeptides. More interestingly, the C-terminus of a nucleopeptide methyl ester 8 was deprotected selectively and in very high yield by papain.l Neither the acetate, the N-terminal urethane, the allyl phosphate, nor the phenylacetamide protection of the nucleobase were attacked (Scheme 17). 

Scheme 17 Selective Deprotection of the C-Terminus of a Nucleopeptide Methyl Ester by Papainb l...

The C-terminus of a nucleopeptide choline ester 9 was deprotectedt smoothly by butyrylcholine esterase (Scheme 19). Neither the acetate, the N-terminal urethane, the allyl phosphate, the phenylacetamide and the peptide bonds, nor the acid- or base-labile purine nucleosides and serine phosphates are attacked. The methods have been exploited further for the synthesis of several biologically relevant nucleopeptides.t ... 

Lipase from wheat germ l and Upase from Aspergillus niger selectively unmasked the methyl and (2-methoxyethoxy)ethyl protected C-terminals of nucleopeptides (Scheme 25). 

Similarly, the respective dipeptide choline esters 34 are readily soluble in purely aqueous media (i. e. without added cosolvent) and are converted into the corresponding carboxylic acids under the mildest conditions, and without side attack on the peptide bonds and the N-terminal urethanes, by means of the commercially available butyrylcholine esterase from horse serum. The increased hydrophilicity of peptide choline esters was used advantageously used for the synthesis of peptides and very sensitive peptide conjugates such as lipidated peptides1118-1211, phosphorylated and glycosylated peptides158, 591 and nucleopeptides (Fig. 18-13)176, 781. 

Several other handles and resins allow cleavage by base-catalyzed (B-elimination reactions [39-42]. The 2-(2-nitrophenyl)e liyl handle 10 has been used for the synthesis of protected peptides and nucleopeptides [43,44]. Cleavage can be accomplished in high yield on treatment with 0.1 m 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) in dioxane, or 20% piperidine in DMF, for 2 h at room temperature. 

A model nucleopeptide (20S) has been prepared which has a phosphodiester bond between... 

Use for Sugar Phosphate, Phospholipid, or Phosphopeptide Synthesis.- A review has been published on the synthesis of phosphorylated biomolecules by the phosphoramidite approach. It contains chapters on sterol-mononucleotide conjugates, mononucleotide glycoconjugates, sugar phosphates, phospholipids, phosphopeptides, and nucleopeptides. 

Many DNAzymes catalyse RNA ligation reactions to yield linear, branched, and lariat-type reaction products. The ligation of DNA strands as well as the phosphorylation of DNA or RNA oligonucleotides was described. Some notable extensions beyond phosphodiester chemistry include a photoreversion reaction, a deglycosylation, porphyrin metalation, nucleopeptide bond formation, and finally a Diels-Alder reaction. This latter reaction is essentially the same studied by the Jaschke lab with RNA as a catalyst (as discussed below in more detail), and the information published to-date indicates that the catalytic proficiency of DNA and RNA enzymes for Diels-Alder reactions is very similar. 

Nucleoproteins or nucleopeptides are compounds consisting of a nucleic acid component and protein component (nucleoproteins) or peptide component. Relatively low-molecular-weight proteins or peptides are... 

---