Facile synthesis of peptide nucleic acids and peptide nucleic acid-peptide conjugates on an automated peptide synthesizer.
Peptide nucleic acids (PNAs) are DNA mimics with a neutral peptide backbone instead of the negatively charged sugar phosphates. PNAs exhibit several attractive features such as high chemical and thermal stability, resistance to enzymatic degradation, and stable binding to their RNA or DNA targets in a sequence-specific manner. Therefore, they are widely used in molecular diagnosis of antisense-targeted therapeutic drugs or probes and in pharmaceutical applications. However, the main hindrance to the effective use of PNAs is their poor uptake by cells as well as the difficult and laborious chemical synthesis. In order to achieve an efficient delivery of PNAs into cells, there are already many published reports of peptides being used for transport across the cell membrane. In this protocol, we describe the automated as well as cost-effective semi-automated synthesis of PNAs and PNA-peptide constructs on an automated peptide synthesizer. The facile synthesis of PNAs will be helpful in generating PNA libraries usable, e.g. for high-throughput screening in biomolecular studies. Efficient synthetic schemes, the automated procedure, the reduced consumption of costly reagents, and the high purity of the products are attractive features of the reported procedure.
High-Field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Spemannstrasse 41, 72076 Tuebingen, Germany. rajendra.joshi@tuebingen.mpg.de
Rajendra
R
Joshi
Deepti
D
Jha
Wu
W
Su
Joern
J
Engelmann
D001331:Automation; D001483:Base Sequence; D008969:Molecular Sequence Data; D015394:Molecular Structure; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
D020135:Peptide Nucleic Acids; D010455:Peptides