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    
Abstract/OtherAbstract:
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.
Authors:
Simone Zaramella; Esther Yeheskiely; Roger Strömberg
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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    
Affiliation:
Division of Organic and Bioorganic Chemistry, MBB, Scheele Laboratory, Karolinska Institutet, S-17177 Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Acylation
Chemistry, Organic / methods
Oligonucleotides / chemical synthesis*
Peptides / chemical synthesis*
Chemical
Reg. No./Substance:
0/Oligonucleotides; 0/Peptides

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


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