Backbone amide linker strategy: protocols for the synthesis of C-terminal peptide aldehydes

Anne Pernille Tofteng Shelton, Knud Jørgen Jensen

Abstract

In the backbone amide linker (BAL) strategy, the peptide is anchored not at the C-terminus but through a backbone amide, which leaves the C-terminal available for various modifications. This is thus a very general strategy for the introduction of C-terminal modifications. The BAL strategy was originally developed using a trisalkoxybenzyl linker, but since then range linkers (handles) with different properties have also been developed. The BAL anchoring is established by anchoring an aromatic aldehyde, typically a trisalkoxybenzaldehyde, to the solid support, followed by attachment of the first amino acid residue by reductive amination. This can be used as a general approach for the introduction of other C-terminal modifications as well as functionalities, such as fluorophors. The second step is an acylation of a secondary amine, followed by standard Fmoc-based solid-phase synthesis to assemble the final peptide. One useful application of this strategy is in the synthesis of C-terminal peptide aldehydes. The C-terminal aldehyde is masked as an acetal during synthesis and then conveniently demasked in the final cleavage step to generate the free aldehyde. Another application is in the synthesis of peptide thioesters with a C-terminal glycine.
Original languageEnglish
Title of host publicationPeptide synthesis and applications
EditorsKnud J. Jensen, Pernille T. Shelton, Søren L. Pedersen
Number of pages9
PublisherHumana Press
Publication date2013
Pages131-139
ISBN (Print)978-1-62703-543-9
ISBN (Electronic)978-1-62703-544-6
DOIs
Publication statusPublished - 2013
SeriesMethods in Molecular Biology
Volume1047
ISSN1064-3745

Cite this