ol7b02455_si_001.pdf (18.48 MB)
Bulky Dehydroamino Acids Enhance Proteolytic Stability and Folding in β‑Hairpin Peptides
journal contribution
posted on 2017-09-14, 15:04 authored by Ankur Jalan, David W. Kastner, Kei G. I. Webber, Mason S. Smith, Joshua L. Price, Steven L. CastleThe 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.