Highly Efficient Synthesis of Peptide–Oligonucleotide Conjugates: Chemoselective Oxime and Thiazolidine Formation

✍ Scribed by Damien Forget; Didier Boturyn; Eric Defrancq; Jean Lhomme; Pascal Dumy

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 162 KB
• Volume: 7
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/1521-3765(20010917)7:18<3976::aid-chem3976>3.0.co;2-x

✦ Synopsis

A convergent strategy for the synthesis of peptide ± oligonucleotide conjugates (POC) is presented. Chemoselective ligation of peptide to oligonucleotide was accomplished by oxime and thiazolidine formation. Oxime conjugation was performed by treating an oxyamine-containing peptide with an aldehyde-containing oligonucleotide or vice versa. Ligation by thiazolidine forma-tion was achieved by coupling a peptide, acylated with a cysteine residue, to an oligonucleotide that was derivatised by an aldehyde function. For both approaches, the conjugates were obtained in good yield without the need for a protection strategy and under mild aqueous conditions. Moreover, the oxime ligation proved useful for directly conjugating duplex oligonucleotides. Combined with molecular biology tools, this methodology opens up new prospects for post-functionalisation of highmolecular-weight DNA structures.