A series of novel peptide N-caps was designed with an emphasis on ease of synthesis and an abundance of hydrogen bond acceptors. Different scaffolds based on sugars, cyclic hydrocarbons, and amino acids are developed with a variety of hydrogen bond acceptors including esters, carboxyls, amides and a sulfonic acid. The efficient use in solid-phase peptide synthesis was demonstrated by incorporating the N-caps to a resin-bound model peptide. Their differential helix nucleating power in aqueous buffer was determined by CD studies. Increases in peptide helicity to a significant extent are observed, leading to a discussion of N-capping efficiency versus ease of synthesis. The potential of the elaborated N-caps for the reversal of β-sheet to α-helix conformations in the context of fibrillogenesis is discussed.
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Notes
Compound 5 was a generous gift from Prof. Klaus Müller, Hoffmann-La Roche, Basel.
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This work was supported by the Swiss National Science Foundation and Debiopharm S.A., Lausanne.
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Mimna, R., Tuchscherer, G. & Mutter, M. Toward the Design of Highly Efficient, Readily Accessible Peptide N-caps for the Induction of Helical Conformations. Int J Pept Res Ther 13, 237–244 (2007). https://doi.org/10.1007/s10989-006-9073-9
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DOI: https://doi.org/10.1007/s10989-006-9073-9