Examining the Effect of an Anion-Binding Reagent on the Structure of Deprotonated Leucine Enkephalin Using Cryogenic-Ion Infrared Action Spectroscopy

Biomolecular systems feature a complex interaction network
comprising
numerous intra- and intermolecular interactions. By isolating biomolecules
under vacuum conditions, the intricate balance between specific interaction
motifs can be characterized with precise control over conditions.
In this study, we apply cryogenic-ion infrared action spectroscopy
and electronic structure methods to examine the structural changes
in the deprotonated form of the model peptide leucine enkephalin (YGGFL)
upon complexation with diserinol isophthalamide (DIP), an anion-binding
reagent. The low-energy conformer of the uncomplexed, deprotonated
peptide ([YGGFL - H]−) adopts a noncanonical turn
structure stabilized by intramolecular ionic hydrogen bonding to the
C-terminal carboxylate moiety. Despite the favorability of DIP to
strongly coordinate with carboxylate residues, we find that the structure
of the peptide is largely unaffected by the binding of DIP. Instead,
DIP only partially coordinates with the carboxylate moiety and is
positioned below the backbone turn of YGGFL to engage in additional
hydrogen bonding interactions. These findings underscore the stability
of the turn structure and the strong energetic penalty imposed by
disruption of this motif even when strong intermolecular coordination
is expected.