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Engineering ?-sheets employing N-methylated heterochiral amino acids.

ABSTRACT: There is a lack of functional group diversity in the reverse turn motifs nucleating a ?-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 ?-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 ?II' turn inducing the ?-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 ?-hairpin.

SUBMITTER: Ghosh D

PROVIDER: S-EPMC5784515 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Engineering β-sheets employing <i>N</i>-methylated heterochiral amino acids.

Ghosh Dipan D Lahiri Priyanka P Verma Hitesh H Mukherjee Somnath S Chatterjee Jayanta J

Chemical science 20160421 8

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 <i>N</i>-methylation of heterochiral amino acids in linear peptides nucleates β-sheet conformation without the necess ...[more]

PMID: 29449932

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