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).
Bibliographical noteFunding 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 Ultraex MALDI-TOF/TOF instrument (EP/K03927X/1), and the BBSRC/EPSRC-funded BrisSynBio (BB/L01386X1) for access to its peptide synthesisers.
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