Nucleopeptide synthesis

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. 

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

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 ... 

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. 

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. 

Current biochemical literature is replete with good reasons for undertaking the synthesis of various nucleopeptides. However, there still seems to be a dearth of activity in this field which is so pertinent to some verj fundamental aspects of cell chemistry. Synthetic studies in 1971 ranged from an interesting approach to pyrimidinyl- and purinyl-peptides by the Pandit group to analogs of the new polyoxin (Chart 18) nucleopeptide antibiotics. One of the natural products, polyoxin M, (Chart 18) has been found to be a powerful inhibitor of yeast chitin synthetase, but several analogs prepared without the 5 -carboxyl and/or the 4"-hydroxyl were inactive in terms of antibiotic activity. 

Robll994 Robles, J., Pedroso, E. and Grandas, A., Stepwise Solid-Phase Synthesis of the Nucleopeptide Phac-Phe-Val-Ser(p ACT)-Gly-OH, J. Org. Chem., 59 (1994) 2482-2486. 

Figure 31 An alternative chemoenzymatic approach to the synthesis of nucleopeptides.

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