Native Chemical Ligation Directed by Photocleavable Peptide Nucleic Acid (PNA) Templates. (2nd November 2017)

• Record Type: Journal Article
• Authors: Middel, Stephen; Panse, Cornelia H.; Nawratil, Swantje; Diederichsen, Ulf
• Is Part Of: Chembiochem. Volume 18:Number 23(2017)
• Page Start: 2328
• Page End: 2332
• Publication Date: 2017-11-02
• Subjects: native chemical ligation -- peptide nucleic acids -- peptides -- photochemistry -- template synthesis; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201700487
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: A novel peptide–peptide ligation strategy is introduced that has the potential to provide peptide libraries of linearly or branched coupled fragments and will be suited to introduce simultaneous protein modifications at different ligation sites. Ligation is assisted by templating peptide nucleic acid (PNA) strands, and therefore, ligation specificity is solely encoded by the PNA sequence. PNA templating, in general, allows for various kinds of covalent ligation reactions. As a proof of principle, a native chemical ligation strategy was elaborated. This PNA‐templated ligation includes easy on‐resin procedures to couple linkers and PNA to the respective peptides, and a traceless photocleavage of the linker/PNA oligomer after the ligation step. A 4, 5‐dimethoxy‐2‐nitrobenzaldehyde‐based linker that allowed the photocleavable linkage of two bio‐oligomers was developed. Abstract : Get in position ! A template‐directed native chemical ligation strategy of applying photocleavable peptide nucleic acid (PNA) strands is presented. PNA/peptide hybrids, connected through a photocleavable linker, assemble by PNA base pairing and the reactive centers are brought in close proximity to facilitate ligation. The templating PNA oligomers can then be cleaved by irradiation.