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Conformation-Specific Infrared and Ultraviolet Spectroscopy of Cold [YAPAA+H]+ and [YGPAA+H]+ Ions: A Stereochemical “Twist” on the β‑Hairpin Turn
journal contribution
posted on 2017-03-29, 00:00 authored by Andrew
F. DeBlase, Christopher P. Harrilal, John T. Lawler, Nicole L. Burke, Scott A. McLuckey, Timothy S. ZwierIncorporation
of the unnatural d-proline (DP) stereoisomer into
a polypeptide sequence is a typical strategy
to encourage formation of β-hairpin loops because natural sequences
are often unstructured in solution. Using conformation-specific IR
and UV spectroscopy of cold (≈10 K) gas-phase ions, we probe
the inherent conformational preferences of the DP and LP diastereomers in the protonated peptide [YAPAA+H]+, where only intramolecular interactions are possible. Consistent
with the solution-phase studies, one of the conformers of [YADPAA+H]+ is folded into a charge-stabilized β-hairpin
turn. However, a second predominant conformer family containing two
sequential γ-turns is also identified, with similar energetic
stability. A single conformational isomer of the LP diastereomer,
[YALPAA+H]+, is found and assigned to a structure
that is not the anticipated “mirror image” β-turn.
Instead, the LP stereocenter promotes a cis-alanine–proline amide bond. The assigned structures contain
clues that the preference of the DP diastereomer to support
a trans-amide bond and the proclivity of LP for a cis-amide bond is sterically driven and
can be reversed by substituting glycine for alanine in position 2,
forming [YGLPAA+H]+. These results provide a
basis for understanding the residue-specific and stereospecific alterations
in the potential energy surface that underlie these changing preferences,
providing insights to the origin of β-hairpin formation.