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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 20102D IR Spectroscopy of Oligopeptides ConformationallyRestrained by C α,α -Dialkylated Glycyl ResiduesHiroaki Maekawa 1 , Matteo De Poli 2 , Gema Ballano 2 ,Fernando Formaggio 2 , Claudio Toniolo 2 , and Nien-Hui Ge 11 Department of Chemistry, University of California at Irvine, Irvine, 92697-2025, CA,U.S.A.; 2 ICB, Padova Unit, CNR, Department of Chemistry, University of Padova,Padova, 35131, ItalyIntroductionRecent advances in ultrafast two-dimensional infrared (2D IR) spectroscopy havedemonstrated its unique capabilities in elucidating peptide structures. To develop thesetechniques with full rigor and to establish spectrum-structure relationships, studies ofmodel systems are needed. To this end, oligopeptides composed of C α,α -dialkylated Glyresidues serve as ideal model systems because of their well-defined peptide backboneconformations. Here, we report the amide-I/II 2D IR spectra of two series of peptides inCDCl 3 solution: (1) unlabeled and ( 13 C=O 18 -Leu and 15 N-Gly) isotope labeled Aib-richhexapeptides, Z-Aib-L-Leu-(Aib) 2 -Gly-Aib-OtBu (Z, benzyloxycarbonyl; Aib,α−aminoisobutyric acid; OtBu: tert-butoxy) and (2) Ac-(Deg) n -OtBu (Ac, acetyl; Deg,C α,α -diethylglycine, n = 2–5). We demonstrate how 2D IR spectral signatures reveal theunderlying 3 10 -helical conformation [1] in peptides (1) and fully-extended (multiple C 5 )conformation [2] in peptides (2).Results and DiscussionIn the study of Aib-rich hexapeptides,a novel isotopelabeling scheme was devised toprobe vibrational couplingsbetween amide-I and -II modeson specific residues. The 2D IRspectra of 13 C=O 18 -Leu monolabeledand13 C=O 18 -Leu/ 15 N-Gly bis-labeled isotopologues(Figure 1) exhibit isotopedependentamide-I/II crosspeaks, clearly indicating that thesecond and fourth peptidelinkages are vibrationallycoupled as they are inproximity, forming a 3 10 -helicalturn. Theoretical calculations,based on an expandedvibrational exciton model,reasonably reproduce theexperimental results. Incontrast, the semi-extended,poly-(Pro) n type II-like structureis predicted to exhibit noisotope shifts in the amide-I/IIcross peaks. This conformationalsensitivity indicates that2D IR is promising for detectingnascent helix formation.Fig. 1. Amide-I/II region of the experimental andcalculated 2D IR spectra of unlabeled (1), 13 C=O 18 -Leu mono-labeled (1*) and 13 C=O 18 -Leu/ 15 N-Gly bislabeled(1**) hexapeptides. The 15 N substitution redshiftsthe amide I/II cross peaks.11*1**602