Neutral Peptides in the Gas Phase: Conformation and Aggregation Issues

Abstract

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...

N–H⋯X interactions stabilize intra-residue C5 hydrogen bonded conformations in heterocyclic α-amino acid derivatives

“…Solid samples were vaporized using laser-desorption to provide isolated molecules at a high temperature which were cooled down rapidly by adiabatic expansion, with two consequences. 34,35 Firstly, interconversion between backbone families (which involves high energy barriers) no longer occurred, leaving a conformational distribution which was representative of the compound at an intermediate temperature (typically room temperature). Secondly, rotational and vibrational cooling within each backbone family funnelled the population to the most stable conformers.…”

“…The conformers obtained in this way were characterized fastidiously using an arsenal of sophisticated laser methods, 34,35 as follows. The sensitivity of the UV spectrum of the Cbz-cap to the molecular conformation allowed us to observe narrow UV spectral signatures in the origin region of the rst pp* transition of the phenyl group, providing a panorama of the conformational diversity.…”

Advancing Inorganic Coordination Chemistry by Spectroscopy of Isolated Molecules: Methods and Applications

“… [120] Much has been done with these methods to study organic and biochemical compounds, for example peptides and biomimetica and as reviewed recently. [121] Few TM complexes have been investigated with such schemes. The R2PI method in itself has of course been systematically and extensively applied for the determination of bond dissociation energies of various heterogeneous TM dimers and related compounds in isolation.…”

Conformational analysis by UV spectroscopy: the decisive contribution of environment-induced electronic Stark effects

“…Conformer-selective UV spectra may be recorded by using UV/UV double resonance techniques, 10 but conformer-selection can also be achieved using ion mobility. 11 Otherwise, UV chromophores take a critical part in the conformer-selection process for other types of spectroscopy, like conformer-selective IR [12][13][14] or photoinduced dynamics, 15 and in the measurement of the fractional abundances of a conformational mixture, 16 which can be considered as the ultimate goal of conformational analysis.…”