Bulky Dehydroamino Acids Enhance Proteolytic Stability and Folding in β‑Hairpin Peptides

The bulky dehydroamino acids dehydrovaline (ΔVal) and dehydro­ethyl­norvaline (ΔEnv) can be inserted into the turn regions of β-hairpin peptides without altering their secondary structures. These residues increase proteolytic stability, with ΔVal at the (i + 1) position having the most substantial i...

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Bibliographic Details
Published in:Organic letters 2017-10, Vol.19 (19), p.5190-5193
Main Authors: Jalan, Ankur, Kastner, David W, Webber, Kei G. I, Smith, Mason S, Price, Joshua L, Castle, Steven L
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acids
Hydrogen Bonding
Models, Molecular
Molecular Structure
Peptides - chemistry
Protein Folding
Protein Structure, Secondary
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Summary:The bulky dehydroamino acids dehydrovaline (ΔVal) and dehydro­ethyl­norvaline (ΔEnv) can be inserted into the turn regions of β-hairpin peptides without altering their secondary structures. These residues increase proteolytic stability, with ΔVal at the (i + 1) position having the most substantial impact. Additionally, a bulky dehydroamino acid can be paired with a d-amino acid (i.e., d-Pro) to synergistically enhance resistance to proteolysis. A link between proteolytic stability and peptide structure is established by the finding that a stabilized ΔVal-containing β-hairpin is more highly folded than its Asn-containing congener.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.7b02455