PEPTIDE-OLIGONUCLEOTIDE HYBRIDS WITH N-ACYLPHOSPHORAMIDATE LINKAGES

被引:17
作者
ROBLES, J
PEDROSO, E
GRANDAS, A
机构
[1] Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, 08028 Barcelona
关键词
D O I
10.1021/jo00120a032
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The preparation of a peptide-oligonucleotide hybrid with an N-acylphosphoramidate linkage has been carried out by (i) phosphitylation of the C-terminal carboxamide of a protected peptide by reaction with a chloroalkoxy(dialkylamino)phosphine in the presence of a base, (ii) coupling of the resulting N-acylphosphorodiamidite onto an oligonucleotide-resin followed by oxidation, and (iii) deprotection and cleavage under basic conditions. The synthetic method takes advantage of the unprecedented reaction of primary carboxamides with electrophilic P-III species and takes place under mild conditions which are compatible with the stability of both the peptide and the oligonucleotide components.
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页码:4856 / 4861
页数:6
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