title: Gas-Phase Folding of a Prototypical Protonated Pentapeptide: Spectroscopic Evidence for Formation of a Charge-Stabilized β-Hairpin.
abstract: Ultraviolet and infrared-ultraviolet (IR-UV) double-resonance photofragment spectroscopy has been carried out in a tandem mass spectrometer to determine the three-dimensional structure of cryogenically cooled protonated C-terminally methyl esterified leucine enkephalin [YGGFL-OMe+H](+). By comparing the experimental IR spectrum of the dominant conformer with the predictions of DFT M05-2X/6-31+G(d) calculations, a backbone structure was assigned that is analogous to that previously assigned by our group for the unmodified peptide [ Burke, N.L.; et al. Int. J. Mass Spectrom. 2015 , 378 , 196 ], despite the loss of a C-terminal OH binding site that was thought to play an important role in its stabilization. Both structures are characterized by a type II' β-turn around Gly(3)-Phe(4) and a γ-turn around Gly(2), providing spectroscopic evidence for the formation of a β-hairpin hydrogen bonding pattern. Rather than disrupting the peptide backbone structure, the protonated N-terminus serves to stabilize the β-hairpin by positioning itself in a pocket above the turn where it can form H-bonds to the Gly(3) and C-terminus C═O groups. This β-hairpin type structure has been previously proposed as the biologically active conformation of leucine enkephalin and its methyl ester in the nonpolar cell membrane environment [ Naito, A.; Nishimura, K. Curr. Top. Med. Chem. 2004 , 4 , 135 - 143 ].
authors: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors: Nicole L
authors: NL
authors: Burke
authors: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors: Andrew F
authors: AF
authors: DeBlase
authors: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors: James G
authors: JG
authors: Redwine
authors: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors: John R
authors: JR
authors: Hopkins
authors: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors: Scott A
authors: SA
authors: McLuckey
authors: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors: Timothy S
authors: TS
authors: Zwier
mesh_terms: D004355:Drug Stability; D004743:Enkephalin, Leucine / Q000737:chemistry*; D005740:Gases / Q000737:chemistry; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D005740:Gases; D009842:Oligopeptides; D004743:Enkephalin, Leucine