Issue 8, 2016

Engineering β-sheets employing N-methylated heterochiral amino acids


There is a lack of functional group diversity in the reverse turn motifs nucleating a β-sheet conformation in designed peptides, proteins and foldamers. The majority of these sequences consist of D-Pro–L-Pro, D-Pro–Gly or Asn–Gly as the turn inducing motif restricting their biological application and physicochemical modulation. In this report, for the first time we elucidate that N-methylation of heterochiral amino acids in linear peptides nucleates β-sheet conformation without the necessity of having a ring or covalent constraint at the reverse turn. Our results show that D-Pro can be conveniently substituted by any other N-methylated D-amino acid followed by an N-methylated L-amino acid or sarcosine to adopt a βII′ turn inducing the β-sheet folding. Furthermore, we reveal that a single amino acid either at the i + 1 or i + 2 site of the reverse turn can modulate the right-handed twist, which eventually dictates the extent of the foldedness of the β-hairpin.

Graphical abstract: Engineering β-sheets employing N-methylated heterochiral amino acids

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Article information

Article type
Edge Article
02 Feb 2016
19 Apr 2016
First published
21 Apr 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 5212-5218

Engineering β-sheets employing N-methylated heterochiral amino acids

D. Ghosh, P. Lahiri, H. Verma, S. Mukherjee and J. Chatterjee, Chem. Sci., 2016, 7, 5212 DOI: 10.1039/C6SC00518G

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