Search Results (5)

Peptides are an important class of biomolecules that perform many physiological functions and which occupy a significant and increasing share of the pharmaceutical market. Methods to determine the solid-state structures of peptides in different environments are important to help understand their biological functions and to aid the development of drug formulations. Here, a new magic-angle spinning (MAS) solid-state nuclear magnetic resonance (SSNMR) approach is described for the structural analysis of uniformly ¹³C-labeled solid peptides. Double-quantum (DQ) coherence between selective pairs of ¹³C nuclei in peptide backbone and side-chain CH₃ groups is excited to provide restraints on (i) ¹³C–¹³C internuclear distances and (ii) the relative orientations of C–H bonds. DQ coherence is selected by adjusting the MAS frequency to the difference in the resonance frequencies of selected nuclear pairs (the rotational resonance condition), which reintroduces the dipolar coupling between the nuclei. Interatomic distances are then measured using a constant time SSNMR experiment to eliminate uncertainties arising from relaxation effects. Further, the relative orientations of C–H bond vectors are determined using a DQ heteronuclear local field SSNMR experiment, employing ¹³C–¹H coupling amplification to increase sensitivity. These methods are applied to determine the molecular conformation of a uniformly ¹³C-labeled peptide, N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF). From just six distance and six angular restraints, two possible molecular conformations are determined, one of which is in excellent agreement with the crystal structure of a closely related peptide. The method is envisaged to a useful addition to the SSNMR repertoire for the solid-state structure determination of peptides in a variety of forms, including amyloid fibrils and pharmaceutical formulations. Full article

Single and double electron capture cross-sections for collisions of ¹¹⁸Sn⁴⁺ with molecular hydrogen have been measured in an energy range of 1 keV to 16 keV using a crossed-beam setup. The cross-sections are determined from measurements of charge-state-resolved ion currents obtained through a retarding field analyser. Remarkably, the single electron capture cross-sections for Sn⁴⁺ are more than a factor 3 smaller than the previously determined single electron capture cross-sections for Sn³+–H₂ collisions and the double electron capture cross-sections are only about 20% smaller than the single electron capture cross-sections. These results are understood on the basis of potential energy curve crossings. The first active curve crossings for the Sn⁴⁺–H₂ system happen at a relatively small internuclear distance of about 5.5 a.u., which should be compared to 8 a.u. for Sn³+ ions. Multi-channel Landau–Zener calculations have been performed for single electron capture and confirm these low cross-sections. The curve crossing for double electron capture by Sn⁴⁺ lies very close to the one for single electron capture, which may explain the single and double electron capture cross-sections being of similar magnitude. Full article

Background: Nanobodies, or VHHs, are derived from heavy chain-only antibodies (hcAbs) found in camelids. They overcome some of the inherent limitations of monoclonal antibodies (mAbs) and derivatives thereof, due to their smaller molecular size and higher stability, and thus present an alternative to mAbs for therapeutic use. Two nanobodies, Nb23 and Nb24, have been shown to similarly inhibit the self-aggregation of very amyloidogenic variants of β2-microglobulin. Here, the structure of Nb23 was modeled with the Chemical-Shift (CS)-Rosetta server using chemical shift assignments from nuclear magnetic resonance (NMR) spectroscopy experiments, and used as prior knowledge in PONDEROSA restrained modeling based on experimentally assessed internuclear distances. Further validation was comparatively obtained with the results of molecular dynamics trajectories calculated from the resulting best energy-minimized Nb23 conformers. Methods: 2D and 3D NMR spectroscopy experiments were carried out to determine the assignment of the backbone and side chain hydrogen, nitrogen and carbon resonances to extract chemical shifts and interproton separations for restrained modeling. Results: The solution structure of isolated Nb23 nanobody was determined. Conclusions: The structural analysis indicated that isolated Nb23 has a dynamic CDR3 loop distributed over different orientations with respect to Nb24, which could determine differences in target antigen affinity or complex lability. Full article

We present a solid-state nuclear magnetic resonance (NMR) spectroscopy study of the local ${}^{31}$ P and ${}^1$ H environments in monetite [CaHPO ${}_4$ ; dicalcium phosphate anhydrous (DCPA)], as well as their relative spatial proximities. Each of the three ${}^1$ H NMR peaks was unambiguously assigned to its respective crystallographically unique H site of monetite, while their pairwise spatial proximities were probed by homonuclear ${}^1$ H– ${}^1$ H double quantum–single quantum NMR experimentation under fast magic-angle spinning (MAS) of 66 kHz. We also examined the relative ${}^1$ H– ${}^{31}$ P proximities among the inequivalent {P1, P2} and {H1, H2, H3} sites in monetite; the corresponding shortest internuclear ${}^1$ H– ${}^{31}$ P distances accorded well with those of a previous neutron diffraction study. The NMR results from the monetite phase were also contrasted with those observed from the monetite component present in a pyrophosphate-bearing calcium phosphate cement, demonstrating that while the latter represents a disordered form of monetite, it shares all essential local features of the monetite structure. Full article

The relation between analyticity in mathematics and the concept of a global information field in physics is reviewed. Mathematics is complete in the complex plane only. In the complex plane, a very powerful tool appears—analyticity. According to this property, if an analytic function is known on the countable set of points having an accumulation point, then it is known everywhere. This mysterious property has profound consequences in quantum physics. Analyticity allows one to obtain asymptotic (approximate) results in terms of some singular points in the complex plane which accumulate all necessary data on a given process. As an example, slow atomic collisions are presented, where the cross-sections of inelastic transitions are determined by branch-points of the adiabatic energy surface at a complex internuclear distance. Common aspects of the non-local nature of analyticity and a recently introduced interpretation of classical electrodynamics and quantum physics as theories of a global information field are discussed. Full article