De Novo Design of Immunoglobulin-like Domains

Antibodies and antibody derivatives such as nanobodies contain immunoglobulin-like (Ig) [beta]-sandwich scaffolds which anchor the hypervariable antigen-binding loops and constitute the largest growing class of drugs. Current engineering strategies for this class of compounds rely on naturally existing Ig frameworks, which can be hard to modify and have limitations in manufacturability, designability and range of action. Here we develop design rules for the central feature of the Ig fold architecture - the non-local cross-[beta]; structure connecting the two [beta]-sheets - and use these to de novo design highly stable seven-stranded Ig domains, confirm their structures through X-ray crystallography, and show they can correctly scaffold functional loops. Our approach opens the door to the design of a new class of antibody-like scaffolds with tailored structures and superior biophysical properties.

Chiral zeolite beta: structure, synthesis, and application

Pure polymorph-A of zeolite beta with chiral pore structure has potential applications in asymmetric catalysis and chiral separations.

Correction: Chiral zeolite beta: structure, synthesis, and application

Correction for ‘Chiral zeolite beta: structure, synthesis, and application’ by Tingting Lu et al., Inorg. Chem. Front., 2019, DOI: 10.1039/c9qi00574a.

Spectroscopic investigation of the effect of polyphenolic compounds on the amyloid-[beta] protein

Aggregation of the amyloid-[beta] (A[beta]) protein is associated with the development of Alzheimer's disease. A[beta] is a 39-43 residue cleavage product of the amyloid precursor protein (APP). A[beta] aggregates to produce insoluble plaques in the brain, which are composed of cross [beta]-sheet structured fibrils. Various polyphenolic compounds, both naturally occurring and synthetic, have been shown to interfere with A[beta] aggregation. To evaluate the ability of specific polyphenols to prevent A[beta] aggregation, this investigation utilized nordihydroguaiaretic acid, curcumin, rosmarinic acid, resveratrol, piceatannol, and diethylstilbestrol. These polyphenols differ in the number of ring substituents and the atom linker between the rings. The interaction of A[beta] with the polyphenolic compounds was analyzed using circular dichroism (CD) and deep ultraviolet resonance Raman (dUVRR) spectroscopies. The polyphenols diethylstilbestrol, resveratrol, and piceatannol have increasing numbers of hydroxyl substituents on their rings, having two, three, and four respectively. It was found that with increasing number of hydroxyl ring substituents, the protein remained predominantly disordered and prevented formation of [beta]-structure in the protein and aided in the destabilization of pre-formed A[beta] fibrils. Decreasing the number of hydroxyl substituents increases the likelihood of [beta]-sheet formation, prevented destabilization of pre-formed A[beta] fibrils, and induced loss of stability of the protein. The polyphenols nordihydroguaiaretic acid, curcumin, and rosmarinic acid have increasing polarity respectively in the chain linker between the phenolic rings. Each of these polyphenols have four ring substituents and have four to six atoms in their chain linker. It was found that with increasing the polarity of the linker, the protein had a greater tendency to form a [beta]-structure, however pre-formed A[beta] fibrils were destabilized efficiently by all three polyphenols. Though a nonpolar chain linker pushed fibrillar protein toward a more disordered structure initially, the final state was similar regardless of added polyphenol.

The Influence of Heat Treatment on the Structure and Microstructure of Ti-15Mo-xNb System Alloys for Biomedical Applications

The Ti-15Mo-xNb system integrates a new class of titanium alloys without the presence of aluminum and vanadium, which exhibit cytotoxicity, and that have low elasticity modulus values (below 100 GPa). This occurs because these alloys have a beta structure, which is very attractive for use as biomaterials. In addition, Brazil has about 90% of the world’s resources of niobium, which is very important economically. It strategically invests in research on the development and processing of alloys containing this element. In this paper, a study of the influence of heat treatments on the structure and microstructure of the alloys of a Ti-15Mo-xNb system is presented. The results showed grain grown with heat treatment and elongated and irregular grains after lamination due to this processing. After quenching, there were no changes in the microstructure in relation to heat-treated and laminated conditions. These results corroborate the x-ray diffraction results, which showed the predominance of the β phase.

NXO beta structure mimicry: an ultrashort turn/hairpin mimic that folds in water

An NXO building block derived tetrapeptide mimic emulates a natural proline-glycine β-turn/hairpin in polar media, including water at room temperature.

Modeling of the Temperature Distribution in Machining TC4 Titanium Alloy

As one of the most commonly used titanium alloys, TC4 (Ti6Al4V) has an alpha–beta structure and is widely used for aircraft components. In this study, numerical simulation was conducted by using FEM software on the whole cutting process for TC4 alloy mounting parts in an effort to investigate the metal flow behavior. This study not only helps to understand but also to improve and optimize cutting process, which are based on experience combined with a trial-and-error approach.