Single-conformation spectroscopy of cold, protonated DPG-containing peptides: switching β-turn types and formation of a sequential type II/II′ double β-turn. Issue 4 (12th January 2022)

• Record Type: Journal Article
• Authors: Lawler, John T.; Harrilal, Christopher P.; DeBlase, Andrew F.; Sibert, Edwin L.; McLuckey, Scott A.; Zwier, Timothy S.
• Is Part Of: Physical chemistry chemical physics. Volume 24:Issue 4(2022)
• Page Start: 2095
• Page End: 2109
• Publication Date: 2022-01-12
• Subjects: Chemistry, Physical and theoretical -- Periodicals; 541.3
• DOI: 10.1039/d1cp04852j
• Languages: English
• ISSNs: 1463-9076

Abstract

Abstract : Protonated D P and L P diastereomers of the pentapeptide YAPGA were examined with IR–UV spectroscopy for their ability to form β-turns. Abstract : d -Proline ( D Pro, D P) is widely utilized to form β-hairpin loops in engineered peptides that would otherwise be unstructured, most often as part of a D PG sub-unit that forms a β-turn. To observe whether D PG facilitated this effect in short protonated peptides, conformation specific IR–UV double resonance photofragment spectra of the cold (∼10 K) protonated D P and L P diastereomers of the pentapeptide YAPGA was carried out in the hydride stretch (2800–3700 cm −1 ) and amide I/II (1400–1800 cm −1 ) regions. A model localized Hamiltonian was developed to better describe the 1600–1800 cm −1 region commonly associated with the amide I vibrations. The CO stretch fundamentals experience extensive mixing with the N–H bending fundamentals of the NH3 + group in these protonated peptides. The model Hamiltonian accounts for experiment in quantitative detail. In the D P diastereomer, all the population is funneled into a single conformer which presented as a type II β-turn with A and D P in the i + 1 and i + 2 positions, respectively. This structure was not the anticipated type II′ β-turn across D PG that we had hypothesized based on solution-phase propensities. Analysis of the conformational energy landscape shows that both steric and charge-induced effects play a role in the preferred formation of the type II β-turn. In contrast, the L P isomer forms three conformations with very different structures, none of which were type II/II′ β-turns, confirming that L PG is not a β-turn former. Finally, single-conformation spectroscopy was also carried out on the extended peptide [YAA D PGAAA + H] + to determine whether moving the protonated N-terminus further from D PG would lead to β-hairpin formation. Despite funneling its entire population into a single peptide backbone structure, the assigned structure is not a β-hairpin, but a concatenated type II/type II′ double β-turn that displaces the peptide backbone laterally by about 7.5 Å, but leaves the backbone oriented in its original direction.