Scalable synthesis and coupling of quaternary α-arylated amino acids: α-aryl substituents are tolerated in α-helical peptides

Daniel J Leonard, Francis Zieleniewski, Isabelle Wellhöfer, Emily G Baker, John W Ward, Derek N Woolfson, Jonathan Clayden

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Quaternary amino acids are important tools for the modification and stabilisation of peptide secondary structures. Here we describe a practical and scalable synthesis applicable to quaternary alpha-arylated amino acids (Q4As), and the development of solid-phase synthesis conditions for their incorporation into peptides. Monomeric and dimeric α-helical peptides are synthesised with varying degrees of Q4A substitution and their structures examined using biophysical methods. Both enantiomers of the Q4As are tolerated in folded monomeric and oligomeric α-helical peptides, with the (R)-enantiomer slightly more so than the (S).

Original languageEnglish
Article number9386
Pages (from-to)9386-9390
Number of pages5
JournalChemical Science
Volume12
Issue number27
Early online date9 Jun 2021
DOIs
Publication statusPublished - 21 Jul 2021

Bibliographical note

Funding Information:
This work was supported by the EPSRC through the Bristol Chemical Synthesis Centre for Doctoral Training EP/G036764/1 (studentship to F. Z.) and programme grant EP/P027067 (awarded to JPC), A. P. Møller Lægefonden, Rudolph Als Fon-den, Oticon Fonden and Julie Von Müllens Fonden. DNW held a Royal Society Wolfson Research Merit Award (WM140008). We also thank the University of Bristol School of Chemistry Mass Spectrometry Facility for use of the EPSRC-funded Bruker Ultraex MALDI-TOF/TOF instrument (EP/K03927X/1), and the BBSRC/EPSRC-funded BrisSynBio (BB/L01386X1) for access to its peptide synthesisers.

Publisher Copyright:
© The Royal Society of Chemistry.

Structured keywords

  • BCS and TECS CDTs

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