An Efficient and Versatile Synthesis of BisPNA-Peptide Conjugates Based on Chemoselective Oxime Formation

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• 作者：Philippe Neuner ; Pasquale Gallo ; Laura Orsatti ; Laura Fontana ; and Paolo Monaci
• 刊名：Bioconjugate Chemistry
• 出版年：2003
• 出版时间：March 2003
• 年：2003
• 卷：14
• 期：2
• 页码：276 - 281
• 全文大小：120K
• 年卷期：v.14,no.2(March 2003)
• ISSN：1520-4812

文摘

Oligomers with two identical peptide nucleic acid sequences joined by a flexible hairpin linker (bisPNA)can stably bind to specific DNA sequences without altering plasmid supercoiling, thus offering a uniqueopportunity to attach various functional entities to high molecular weight DNA. Current syntheticapproaches, however, severely limit the possibility to link peptides or other chemical moieties (i.e.,sugars, oligonucleotides, etc.) to bisPNA. Here we report a novel strategy for the synthesis of bisPNA-peptide conjugates in which chemoselective ligation of bisPNA to peptides was accomplished throughoxime formation between an oxy-amine-containing peptide and a bisPNA-methyl ketone (complementary modifications can also be used). The described synthesis is highly efficient, does not requirea protection strategy, and is carried out under mild aqueous conditions. Through this methodologylong peptide sequences in either C to N or N to C polarity can be linked to bisPNA. In addition, thisprotocol makes the conjugation of cysteine-containing peptides feasible and allows disulfide bondformation to be controlled. This same approach can be exploited to link oligonucleotides, sugars, orother chemical entities to bisPNA.