Synthesis of the Proposed Structures of Prevezol C

The first enantioselective synthesis of the proposed relative structures of Prevezol C is reported in 11 linear steps from readily available materials. The unusual <i>syn</i> bromohydrin was installed via a multistep sequence culminating in a diastereoselective geminal dibromide reduction. Discrepancies in the spectral data of the synthetic materials and the natural sample have led to the conclusion that the proposed structures are incorrect

Synthesis of the Proposed Structures of Prevezol C

The first enantioselective synthesis of the proposed relative structures of Prevezol C is reported in 11 linear steps from readily available materials. The unusual <i>syn</i> bromohydrin was installed via a multistep sequence culminating in a diastereoselective geminal dibromide reduction. Discrepancies in the spectral data of the synthetic materials and the natural sample have led to the conclusion that the proposed structures are incorrect

Synthesis of the Proposed Structures of Prevezol C

The first enantioselective synthesis of the proposed relative structures of Prevezol C is reported in 11 linear steps from readily available materials. The unusual <i>syn</i> bromohydrin was installed via a multistep sequence culminating in a diastereoselective geminal dibromide reduction. Discrepancies in the spectral data of the synthetic materials and the natural sample have led to the conclusion that the proposed structures are incorrect

Topological Dynamics of Micelles Formed by Geometrically Varied Surfactants

The molecular architecture of sugar-based surfactants strongly affects their self-assembled structure, i.e., the type of micelles they form, which in turn controls both the dynamics and rheological properties of the system. Here, we report the segmental and mesoscopic structure and dynamics of a series of C16 maltosides with differences in the anomeric configuration and degree of tail unsaturation. Neutron spin-echo measurements showed that the segmental dynamics can be modeled as a one-dimensional array of segments where the dynamics increase with inefficient monomer packing. The network dynamics as characterized by dynamic light scattering show different relaxation modes that can be associated with the micelle structure. Hindered dynamics are observed for arrested networks of worm-like micelles, connected to their shear-thinning rheology, while nonentangled diffusing rods relate to Newtonian rheological behavior. While the design of novel surfactants with controlled properties poses a challenge for synthetic chemistry, we demonstrate how simple variations in the monomer structure can significantly influence the behavior of surfactants

Using SANS with Contrast-Matched Lipid Bicontinuous Cubic Phases To Determine the Location of Encapsulated Peptides, Proteins, and Other Biomolecules

An understanding of the location of peptides, proteins, and other biomolecules within the bicontinuous cubic phase is crucial for understanding and evolving biological and biomedical applications of these hybrid biomolecule–lipid materials, including during in meso crystallization and drug delivery. While theoretical modeling has indicated that proteins and additive lipids might phase separate locally and adopt a preferred location in the cubic phase, this has never been experimentally confirmed. We have demonstrated that perfectly contrast-matched cubic phases in D₂O can be studied using small-angle neutron scattering by mixing fully deuterated and hydrogenated lipid at an appropriate ratio. The model transmembrane peptide WALP21 showed no preferential location in the membrane of the diamond cubic phase of phytanoyl monoethanolamide and was not incorporated in the gyroid cubic phase. While deuteration had a small effect on the phase behavior of the cubic phase forming lipids, the changes did not significantly affect our results

Protein-Eye View of the in Meso Crystallization Mechanism

For evolving biological and biomedical applications of hybrid protein–lipid materials, understanding the behavior of the protein within the lipid mesophase is crucial. After more than two decades since the invention of the in meso crystallization method, a protein-eye view of its mechanism is still lacking. Numerous structural studies have suggested that integral membrane proteins preferentially partition at localized flat points on the bilayer surface of the cubic phase with crystal growth occurring from a local fluid lamellar Lα phase conduit. However, studies to date have, by necessity, focused on structural transitions occurring in the lipid mesophase. Here, we demonstrate using small-angle neutron scattering that the lipid bilayer of monoolein (the most commonly used lipid for in meso crystallization) can be contrast-matched using deuteration, allowing us to isolate scattering from encapsulated peptides during the crystal growth process for the first time. During in meso crystallization, a clear decrease in form factor scattering intensity of the peptides was observed and directly correlated with crystal growth. A transient fluid lamellar Lα phase was observed, providing direct evidence for the proposed mechanism for this technique. This suggests that the peptide passes through a transition from the cubic QII phase, via an Lα phase to the lamellar crystalline Lc phase with similar layered spacing. When high protein loading was possible, the lamellar crystalline Lc phase of the peptide in the single crystals was observed. These findings show the mechanism of in meso crystallization for the first time from the perspective of integral membrane proteins