Synthesis of biologically active peptide nucleic acid-peptide conjugates by sortase-mediated ligation.
Sortase A is a transpeptidase that cleaves at a pentapeptide-motif and subsequently transfers the acyl component to a nucleophile containing N-terminal oligoglycines. We investigate the reaction conditions of the sortase-mediated ligation and demonstrate a useful application by the synthesis of a peptide nucleic acid-cell-penetrating peptide chimera, the reaction equilibrium of which can be shifted in favor of the product by dialyzing out the low molecular weight byproduct. The synthesized conjugate exhibits dose-dependent antisense activity.
Pritz
Stephan
S
Leibniz-Institute of Molecular Pharmacology, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. pritz@fmp-berlin.de
Wolf
Yvonne
Y
Kraetke
Oliver
O
Klose
Jana
J
Bienert
Michael
M
Beyermann
Michael
M
D000595:Amino Acid Sequence; D019881:Aminoacyltransferases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009696:Nucleic Acids / Q000737:chemistry* / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*
D001426:Bacterial Proteins; D009696:Nucleic Acids; D010455:Peptides; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases