Folding properties, handedness control and aggregation behavior of helical aromatic δ-amino acid foldamers in water

Foldamers are an emerging class of molecules inspired by natural biopolymers, that also have the ability to fold into well-defined three-dimensional structures. As shape complementarity dictates many biological processes such as enzyme catalysis, signal transduction, and pathogen recognition, foldamers hold the potential to mimic and even extend the functions observed in proteins and nucleic acids. Over the decades, backbone types have been continually extended from β-peptides, which are still closely related to α-amino acids, to more abiotic oligomers. Aromatic oligoamides and aromatic δ-amino acids, in particular, offer easy synthetic access, amenability to solid phase synthetic methods and high folding propensity leading to helical structures that are very stable in most solvent environments. Thus, side chain positioning and geometry are well predictable, which offers a basis for functional designs. But tertiary and quaternary folds will ultimately be needed to unlock the true scope of these foldamers. This work describes a new family of aromatic δ-amino acid monomers based on 2-(2-aminophe-noxy)acetic acid (B). It was demonstrated that these more flexible units can be combined with the previously known aromatic δ-amino acid building blocks without significantly altering their canon-ical helical fold. The subtle differences in curvature of these units allow a fine-tuning of side chain positioning and stability of a given oligomer by adjusting its monomer composition and sequence order. Furthermore, a chiral B-unit was developed, which—when incorporated in the middle of aromatic helix sequences—proved to be able to bias handedness to over 99% towards one helicity. The monomer also induced handedness when positioned at the second or penultimate position of a sequence, albeit with weaker bias when close to the N-terminus. Thus, this unit enables designs that rely on both handedness control and free N- and C-termini for binding and/or further functionalization. Finally, the work describes the discovery of a binding interface between C-terminal aromatic helix cross sections leading to homochiral dimers in aqueous solution. Although they are based on aromatic stacking, the dimers are discrete, and their binding strength can be controlled by the nature of the side chains that are positioned close to the interface and the pH environment. By utilizing a primary amide terminus on one binding partner, exclusive heterodimer formation was achieved in the right concentration window. This binding interface can be useful in the future design of larger self-assembled structures. Conclusively, these findings represent important tools for the development of more sophisticated foldamer designs in aqueous media. Additionally, preliminary results of the formation of a side-to-side helix-aggregate (which has been a guiding goal throughout the research for this thesis) are presented. Strategies for bundle formation that have been utilized and challenges that still remain are discussed and should serve as a starting point for future designs

Generalizing the Aromatic delta-Amino Acid Foldamer Helix

A series of aromatic oligoamide foldamer sequences containing different proportions of three delta-amino acids derived from quinoline, pyridine, and benzene and possessing varying flexibility, for example due to methylene bridges, were synthesized. Crystallographic structures of two key sequences and H-1 NMR data in water concur to show that a canonical aromatic helix fold prevails in almost all cases and that helix stability critically depends on the ratio between rigid and flexible units. Notwithstanding subtle variations of curvature, i. e. the numbers of units per turn, the aromatic delta-peptide helix is therefore shown to be general and tolerant of a great number of sp(3) centers. We also demonstrate canonical helical folding upon alternating two monomers that do not promote folding when taken separately: folding occurs with two methylenes between every other unit, not with one methylene between every unit. These findings highlight that a fine-tuning of helix handedness inversion kinetics, curvature, and side chain positioning in aromatic delta-peptidic foldamers can be realized by systematically combining different yet compatible delta-amino acids

Design and Development of a Compact Magnetic Bearing Momentum Wheel for Micro and Small Satellites

Reaction and momentum wheels have become standard equipment for three-axis attitude stabilisation of conventional satellite classes as used e.g. for telecommunication and remote sensing missions. Owing to very compact mechanical designs and highly integrated electronics, wheels are now also more and more interesting for small satellites up to 100…200 kg with increasingly demanding requirements on attitude control. Wheels suitable for small satellites have a typical momentum capacity up to approximately 0.4 Nms, and masses up to about 2 kg. All existing miniature wheels known to the authors are relying on ball bearings for rotor suspension, which may limit the lifetime of a particular mission or introduce undesired levels of micro-vibrations. Magnetic bearings have the potential to overcome those disadvantages. However, the design of a sufficiently small magnetic bearing with all the necessary components and sub-assemblies involves a number of technical challenges, which are discussed in detail. The paper focuses on the magnetic bearing design process, using magnetic field CAE tools, and the overall wheel design. A prototype of a compact magnetic bearing wheel currently under construction is presented. Moreover, control aspects of the magnetic bearing and the drive motor design will be described and an outlook for further improvements and potential future developments will be given

Using Satellites to Track Indicators of Global Air Pollution and Climate Change Impacts: Lessons Learned From a NASA‐Supported Science‐Stakeholder Collaborative

The 2018 NASA Health and Air Quality Applied Science Team (HAQAST) "Indicators" Tiger Team collaboration between NASA-supported scientists and civil society stakeholders aimed to develop satellite-derived global air pollution and climate indicators. This Commentary shares our experience and lessons learned. Together, the team developed methods to track wildfires, dust storms, pollen counts, urban green space, nitrogen dioxide concentrations and asthma burdens, tropospheric ozone concentrations, and urban particulate matter mortality. Participatory knowledge production can lead to more actionable information but requires time, flexibility, and continuous engagement. Ground measurements are still needed for ground truthing, and sustained collaboration over time remains a challenge

Generalizing the Aromatic δ‐Amino Acid Foldamer Helix

A series of aromatic oligoamide foldamer sequences containing different proportions of three δ-amino acids derived from quinoline, pyridine, and benzene and possessing varying flexibility, for example due to methylene bridges, were synthesized. Crystallographic structures of two key sequences and 1H NMR data in water concur to show that a canonical aromatic helix fold prevails in almost all cases and that helix stability critically depends on the ratio between rigid and flexible units. Notwithstanding subtle variations of curvature, i. e. the numbers of units per turn, the aromatic δ-peptide helix is therefore shown to be general and tolerant of a great number of sp3 centers. We also demonstrate canonical helical folding upon alternating two monomers that do not promote folding when taken separately: folding occurs with two methylenes between every other unit, not with one methylene between every unit. These findings highlight that a fine-tuning of helix handedness inversion kinetics, curvature, and side chain positioning in aromatic δ-peptidic foldamers can be realized by systematically combining different yet compatible δ-amino acids

Discrete Stacked Dimers of Aromatic Oligoamide Helices

Tight binding was observed between the C-terminal cross section of aromatic oligoamide helices in aqueous solution, leading to the formation of discrete head-to-head dimers in slow exchange on the NMR timescale with the corresponding monomers. The nature and structure of the dimers was evidenced by 2D NOESY and DOSY spectroscopy, mass spectrometry and X-ray crystallography. The binding interface involves a large hydrophobic aromatic surface and hydrogen bonding. Dimerization requires that helices have the same handedness and the presence of a C-terminal carboxy function. The protonation state of the carboxy group plays a crucial role, resulting in pH dependence of the association. Dimerization is also influenced by neighboring side chains and can be programmed to selectively produce heteromeric aggregates

Quantitative helix handedness bias through a single H <i>vs.</i> CH₃ stereochemical differentiation

A single stereogenic center determines the stereochemistry of multiturn aromatic helices and outweighs chiral units that have the opposite effect.</p

Using Satellites to Track Indicators of Global Air Pollution and Climate Change Impacts: Lessons Learned From a NASA-Supported Science-Stakeholder Collaborative.

The 2018 NASA Health and Air Quality Applied Science Team (HAQAST) “Indicators” Tiger Team collaboration between NASA‐supported scientists and civil society stakeholders aimed to develop satellite‐derived global air pollution and climate indicators. This Commentary shares our experience and lessons learned. Together, the team developed methods to track wildfires, dust storms, pollen counts, urban green space, nitrogen dioxide concentrations and asthma burdens, tropospheric ozone concentrations, and urban particulate matter mortality. Participatory knowledge production can lead to more actionable information but requires time, flexibility, and continuous engagement. Ground measurements are still needed for ground truthing, and sustained collaboration over time remains a challenge