The infrared and ultraviolet spectra of a series of capped asparagine-containing peptides, Ac-Asn-NHBn, Ac-Ala-Asn-NHBn, and Ac-Asn-Asn-NHBn, have been recorded under jet-cooled conditions in the gas phase in order to probe the influence of the Asn residue, with its -CH2-C(=O)-NH2 side chain, on the local conformational preferences of a peptide backbone. The double-resonance methods of resonant ion-dip infrared (RIDIR) spectroscopy and infrared-ultraviolet hole-burning (IR-UV HB) spectroscopy were used to record single-conformation spectra in the infrared and ultraviolet, respectively, free from interference from other conformations present in the molecular beam. Ac-Asn-NHBn spreads its population over two conformations, both of which are stabilized by a pair of H-bonds that form a bridge between the Asn carboxamide group and the NH and C=O groups on the peptide backbone. In one the peptide backbone engages in a 7-membered H-bonded ring (labeled C7eq), thereby forming an inverse I-turn, stabilized by a C6/C7 Asn bridge. In the other the Asn carboxamide group forms a C8/C7 H-bonded bridge with the carboxamide group facing in the opposite direction across an extended peptide backbone involving a C5 interaction. Both Ac-Ala-Asn-NHBn and Ac-Asn-Asn-NHBn are found exclusively in a single conformation in which the peptide backbone engages in a type I β-turn with its C10 H-bond. The Asn residue(s) stabilize this β-turn via C6 H-bond(s) between the carboxamide C=O group and the same residue's amide NH. These structures are closely analogous to the corresponding structures in Gln-containing peptides studied previously [Walsh, P. S. et al. PCCP 2016, 18, 11306-11322; Walsh, P. S. et al. Angew. Chem. Int. Ed. 2016, 55, 14618-14622], indicating that the Asn and Gln side chains can each configure so as to stabilize the same backbone conformations. Spectroscopic and computational evidence suggest that glutamine is more predisposed than asparagine to β-turn formation via unusually strong side-chain-backbone hydrogen-bond formation. Further spectral and structural similarities and differences due to the side-chain length difference of these similar amino acids are presented and discussed.
Bibliographical noteFunding Information:
The Purdue authors gratefully acknowledge support for this research from the National Science Foundation (NSF Grant CHE-1456256 and CHE-1764148). J.L. and S.H.C. acknowledge support from the National Research Foundation of Korea (NRF-2016R1A2B4012798).
All Science Journal Classification (ASJC) codes
- Physical and Theoretical Chemistry