Document Detail

A method for solid-phase synthesis of oligonucleotide 5'-peptide-conjugates using acid-labile alpha-amino protections.
MedLine Citation:
PMID:  15506766     Owner:  NLM     Status:  MEDLINE    
We describe the development of a solid-phase technique for the synthesis of 5'-peptide-oligonucleotide conjugates (POCs) with a uniform protection strategy for the nucleic acid and the peptide fragments. On the alpha-amino function, the amino acid building blocks were protected with the 2-(biphenyl-4-yl)propan-2-yloxycarbonyl (Bpoc) group. This protection is removed during the stepwise peptide elongation by the same acidic conditions used for removal of the dimethoxytrityl (DMT) group used in the oligonucleotide assembly (3% trichloroacetic acid, 2 min). The 2-(3,5-dimethoxyphenyl)propan-2-yloxycarbonyl (Ddz) group was also tested. With this somewhat more stable group, a prolonged contact with the acid (at least 16 min) was required for accomplishing complete alpha-amino deprotection, which resulted in some degree of depurination of the acid-sensitive DNA chain. Base-labile acyl protections were adopted for the side-chains of histidine, lysine, and the nucleobase amino functions. These were all removed in the final deblocking step by ammonolysis. This uniform protection scheme for the peptide and the oligonucleotide enabled the total stepwise synthesis of model conjugates in the 3' --> N direction with high efficiency and purity.
Simone Zaramella; Esther Yeheskiely; Roger Strömberg
Related Documents :
7984506 - Molecular forms of circulating atrial natriuretic peptides in human plasma and their me...
3806626 - Synthetic bovine prothrombin precursor 13-29 for studies of vitamin k dependent carboxy...
21956556 - Preparation of glutamate analogues by enzymatic transamination.
20564676 - Hydrophobicity of peptides containing d-amino acids.
1802986 - Enhancement by fatty acids of the rectal absorption of propranolol: in vitro evaluation...
26976 - Kainic acid lesions of the striatum dissociate amphetamine and apomorphine stereotypy: ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  126     ISSN:  0002-7863     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-27     Completed Date:  2004-12-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14029-35     Citation Subset:  IM    
Division of Organic and Bioorganic Chemistry, MBB, Scheele Laboratory, Karolinska Institutet, S-17177 Stockholm, Sweden.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Chemistry, Organic / methods
Oligonucleotides / chemical synthesis*
Peptides / chemical synthesis*
Reg. No./Substance:
0/Oligonucleotides; 0/Peptides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Two-metal ion, Ni(II) and Cu(II), binding alpha-helical coiled coil peptide.
Next Document:  NMR structural analysis of a modular threading tetraintercalator bound to DNA.