Isolated β‐Turn Model Systems Investigated by Combined IR/UV Spectroscopy

Abstract

The functionality of bioactive molecules sensitively depends on their structure. For the investigation of intrinsic structural properties, molecular beam experiments combined with laser spectroscopy have proven to be a suitable tool. Herein we present an analysis of the two isolated tripeptide model systems Ac-Phe-Tyr(Me)-NHMe and Boc-Phe-Tyr(Me)-NHMe. For this purpose, mass-selective combined IR/UV spectroscopy is applied to both substances in a molecular beam experiment. The comparison of the experimental data with DFT calculations, including different functionals as well as dispersion corrections, allows an assignment of both tripeptide models to β-turns formed independently from the protection groups and supported by the interaction of the two aromatic chromophores.

Isolated Neutral Peptides

“…Val and Phe are more bulky residues capable of forming aromatic-alkyl or aromatic-aromatic interactions between side chains which further stabilises the β-turn enough to make it the major conformation observed [82,84,103,111]. In Phe-Phe or Phe-Tyr sequences, this effect is still enhanced by the existence of additional NH-π interactions, which lead to the exclusive observation of the β-turn [103,111].…”

“…Numerous studies on peptides containing one of the three natural aromatic residues followed [46,47,[51][52][53][54][55], the presence of a near-UV chromophore being the tribute to pay to gain the conformer-selectivity brought by the IR/UV double resonance technique. Non-natural residues derived from the natural UV chromophores have also been widely employed [52,111,[119][120][121][122][123][124][125][126][127][128][129]. Beyond this constraining aspect, the UV frequency and FC pattern being sensitive to the interactions involving the aromatic ring, they can provide very useful structural clues (Sect.…”

“…Comparison with benchmark experimental data suggests that real improvements of both the structure description and the energetics are obtained. Errors of the order of a few kJ mol À1 for the 0 K enthalpy and up to 5 kJ mol À1 for the Gibbs energies can be anticipated on systems as large as dipeptides, including those where dispersion plays a decisive shaping role, as in aromatic-containing peptide chains [95,96,99,103,111,112,135,160]. Correlatively, the development of these functionals provides faster calculations, making possible the investigation of even larger systems [53,107,128,134,139].…”

“…Namely, aromatic-aromatic [103,111,112] or aromatic-alkyl [82,94] interactions not only shape the molecule but also impact the conformational landscape by significantly changing the relative conformational energetics. Unfortunately, because of the lack of workable vibrational probe on these groups, these major interactions are only remotely detected through the constraints they bring to the regions where the vibrational probes lie [103].…”

Can far-IR action spectroscopy combined with BOMD simulations be conformation selective?

“…2 Conformation-selective mid-IR spectroscopy in combination with harmonic density functional theory (DFT) calculations has proven to be a powerful tool to this end, and is nowadays applied on a routine-basis. [3][4][5][6] The far-IR region (radiation o 800 cm À1 ) has often been ignored, due to the possible deficiencies of theoretical tools needed to interpret the experimental spectra in this domain. [7][8][9] This far-IR regime not only complements the mid-IR one, but also yields information that is not accessible in the mid-IR region.…”