Structural investigations on a linear isolated depsipeptide: the importance of dispersion interactions

Abstract

In this paper we present the first investigations on an isolated linear depsipetide CyCO-Gly-Lac-NH-PhOMe (cyclohexylcarbonyl-glycine-lactate-2-anisidine abbreviated as MOC) in a molecular beam experiment. Depsipeptides are a special subclass of peptides which contain at least one ester bond replacing a peptide bond. This leads to a different folding behavior and a different biological activity compared to a "normal" peptide. In order to analyze the folding of an isolated depsipeptide on a molecular level a variety of combined IR/UV methods including IR/IR/UV experiments are applied to MOC. Three different isomers are identified in combination with DFT calculations using the hybrid functional B3LYP-D3 with a TZVP basis set. The most stable structure shows a tweezer-like arrangement between the aromatic chromophore and the aliphatic cyclohexyl ring. A characteristic feature of this structure is that it is stabilized by dispersion interactions resulting from CH/π interactions. If dispersion is not taken into account this structural arrangement is no longer a minimum on the potential energy surface indicating the importance of dispersion interactions.

The Structure of Diphenyl Ether–Methanol in the Electronically Excited and Ionic Ground States: A Combined IR/UV Spectroscopic and Theoretical Study

“…The obtained IR radiation was amplified by using an optical parametric amplification (OPA) process in a further LiNbO 3 crystal by using the DFM output and the fundamental ( λ =1064 nm) of the Nd:YAG laser. For the IR photodissociation experiments in the region of 3400–3750 cm −1 , a different laser system was used that contained two KTA (KTiOAsO 4 ) crystals for the OPA process.…”

“…The UV laser radiation was produced by second-harmonic generation in aB BO crystal by using the output of ad ye laser (Sirah, Cobra-Stretch and PrecisionScan) pumped by the second harmonic (l = 532 nm) of a Nd:YAG laser (Innolas, SpitLight 600 and SpitLight 1000). IR radiation in the region of 3050-3750 cm À1 was generated by difference frequency mixing (DFM) in aL iNbO 3 crystal by using the fundamental (l = 1064 nm) of as eeded Nd:YAG laser (Spectra Physics, PRO-230) and the output of ad ye laser (Sirah, PrecisionScan), which was pumped by the second harmonic (l = 532 nm) of the same Nd:YAG laser.T he obtained IR radiation was amplified by using an optical parametric amplification (OPA) process in af urther LiNbO 3 crystal by using the DFM output and the fundamental (l = 1064 nm) of the Nd:YAG laser.F or the IR photodissociation experiments in the region of 3400-3750 cm À1 ,adifferent laser system [34] was used that contained two KTA( KTiOAsO 4 )c rystals for the OPA process.…”

Rationalizing the diversity of amide–amide H-bonding in peptides using the natural bond orbital method

“…Thus in recent gas phase experiments 12 spectroscopists have recorded conformation-selective spectra in the IR and the UV range, making possible the determination of the most stable conformations in flexible molecules, like peptides or foldamer building blocks, and the characterization of their H-bonding content. The wealth of data collected using laser spectroscopy during the past decade 10,11,[13][14][15][16][17][18][19] constitutes an extended set of peptide conformations, with both natural 14,[20][21][22][23][24][25][26][27][28][29] and synthetic - 17,18,30 or - 31,32 peptides, in which two amide groups interact with each other, according to a panel of geometrical approaches modulated by covalent constrains imposed by the peptide backbone. This conformational set can be considered as a sampling of possible amideamide geometrical approaches, mimicking those encountered in the desolvated inner core of proteins.…”

Accurate geometries for “Mountain pass” regions of the Ramachandran plot using quantum chemical calculations

“…For instance relaxation timescales and the conformational exchange processes derived from simulations with each of the four major force field families (including the AMBER FF99SB) differ significantly . We demonstrate how these problems can be overcome by using quantum mechanical (QM) computations, with methodologies that are proven to deliver accurate structures and properties of isolated polypeptides . Similar approaches using first‐principle based data sets have been reported for isolated and cation‐coordinated conformers of proteinogenic amino acids .…”

“…We have applied a B3LYP density functional along with the dispersion correction (D3) and a medium size double‐zeta plus polarization basis set, SNSD . The B3LYP‐D3/SNSD model combines the good description of structural and spectroscopic properties of small amino‐acids and dipeptides with the empirical dispersion correction, which might be important for correct determination of the 3D structure . The B3LYP‐D3 computations have been also applied for AMBER FF99SB reparameterization allowing to deliver an improved AMBER‐type force field for α,α‐dialkylated‐peptides …”