In order to investigate the influence of hydration on the backbone of a peptide or protected amino acid, the successive aggregation of water to Ac-Phe-OMe is analysed by means of IR/UV double resonance spectroscopy. To achieve meaningful results the spectra have been recorded in the region of the amide A and OH stretching vibrations as well as the amide I/II modes. Comparison with ab initio and DFT calculations leads to size-selective structural assignments. Two isomers of the mono- and dihydrated clusters and one isomer of the trihydrated cluster are observed in the molecular beam leading to a formation of the first solvation shell of the backbone. In case of the trihydrated cluster the backbone geometry is remarkably changed compared to the structure of the monomer since a network of water molecules can be formed.

Combined IR and UV laser spectroscopic techniques in molecular beams merged with theoretical approaches have proven to be an ideal tool to elucidate intrinsic structural properties on a molecular level. It offers the possibility to analyze structural changes by successively adding aggregation partners and thus an environment to a molecule. By this, it further makes these techniques a valuable starting point for a bottom-up approach in understanding the forces shaping larger molecular systems. This bottomup approach was successfully applied to neutral amino acids starting around the 1990s. Ever since experimental and theoretical methods developed further and investigations could be extended to larger peptide systems. Beyond, the review gives an introduction to secondary structures and experimental methods as well as a summary on theoretical approaches. Vibrational frequencies being characteristic probes of molecular structure and interactions are especially addressed. Archetypal biologically relevant secondary structures investigated by molecular beam spectroscopy are described and the influences of specific peptide residues on conformational preferences as well as the competition between secondary structures are discussed. Important influences like microsolvation or aggregation behaviour are presented. Beyond the linear α-peptides the main results of structural analysis on cyclic systems as well as on β-and γ-peptides are summarized. Overall, this contribution addresses current aspects of molecular beam spectroscopy on peptides and related species and provides molecular level insights into manifold issues of chemical and biochemical relevance. 45) , non-protected (cf. e.g. 46-48) and protected amino acids (cf. e.g. 49) up to dipeptide models (cf. e.g. 50).In this context, laser spectroscopic techniques combining IR and UV excitations, that one can consider as belonging to the so-called 'action spectroscopies', provide an isomer-selective method of choice to tackle the 87 ) or immunoglobulins (cf. e.g. 88), but they are also found in context with neurodegenerative diseases (cf. e.g. [89][90][91][92][93][94][95] and Section 12). A further structure associated with these diseases (cf. e.g. 96 ) is the β-helix, which presents a protein structure of several parallel β-strands in a helical arrangement with a frequently repetitive amino acid sequence. The structure is stabilized by H-bonds, sometimes ionic interactions or so called protein-protein interactions, which e.g. include electrostatic and hydrophobic effects. Further aspects of peptide structure in gas phase The role of protection groupsWith the unmodified N-and C-terminus amino acids and peptides can exhibit strong preferences for intramolecular H-bonds involving the N-and C-terminus, and can also form intermolecular H-bonds leading to polymer chains. Nevertheless, in a context where the description of the properties of a protein or a long peptide (with respect to its backbone) by smaller peptides is targeted, the introduction of protecting groups at the N-and...

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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.

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.