Structural Analysis of an Isolated Cyclic Tetrapeptide and its Monohydrate by Combined IR/UV Spectroscopy

Abstract

Cyclopeptides are an important class of substances in nature, and their physiological effects are frequently based on the tendency to form bioactive conformations. Therefore the investigation of their structure yields an understanding of their functionalities. Mass-selective combined IR/UV spectroscopy in molecular beam experiments represents an ideal tool for structural analyses on isolated molecules in the gas phase, such as the investigated cyclo[L-Tyr(Me)-D-Pro](2) peptide and its complexes with water. Using the chosen spectroscopic method in combination with DFT calculations, an assignment of a structure with two intramolecular hydrogen bonds for the naked cyclopeptide is possible. For the monohydrated cluster two isomers have to be discussed: in one of them the water molecule is simply attached to the assigned monomer structure as hydrogen donor, whereas the second isomer can be characterized by a water molecule that is inserted into one of the intramolecular hydrogen bonds.

Isolated Neutral Peptides

“…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.…”

“…Few examples of large molecules for which resolved or partly resolved features have been observed. One can cite tri- [80,85,88,106,112,121,124,133,[138][139][140], tetra- [107,129,134] and pentapeptides [89,98,101,107,139], and larger systems up to gramicidins [54,79,89,108]. In all cases, in addition to the potential lack of conformational selectivity, the theoretical investigation required for the assessment is a cumbersome task, which is not always successful.…”

“…Theoretically predicted some time ago [196], experimental illustrations of these effects have been published only quite recently. Several groups have shown that peptides or related flexible molecules undergo a significant structural change upon solvation, as indicated by changes in their H-bonding network [53,55,102,129,136]. One of the most dramatic studies, carried out on a capped amino-acid solvated by one water molecule, documented the effect of microhydration and its dependence on the solvation site occupied by the water molecule for each conformation.…”

“…It has quickly been extended to other species, beyond the simple canonical structures. Short cyclic peptides have been investigated, documenting the cis conformation of the peptide bonds [76,78,129], which is usually too high in energy to be observed in linear peptides. More recently, other peptides, with longer spacers between amide bonds, i.e.…”

First-principles anharmonic quantum calculations for peptide spectroscopy: VSCF calculations and comparison with experiments

“…However, with the increasing size and conformational complexity, structural identifications become more challenging. In recent years, considerable advancements have been made in highresolution measurements of mid-size peptides by using cryogenic cooling of biomolecular ions, [1][2][3][4][5][6] resonance two-photon IR, 7 fluorescence-dip spectroscopy, 8 and by other techniques. [9][10][11][12][13] These advanced methods are capable of yielding the IR spectroscopy of individual conformers which are free from interference from one another.…”