Disruption Of Noncovalent Interactions Research Articles

Biodegradable, ionic thermoelectric composites via self-assembly of dipeptides and deep eutectic solvents

The growing demand for biodegradable conductive composites is driven by the need to mitigate electronic waste and advance bioelectronics for healthcare applications. Self-assembled peptide composites, particularly diphenylalanine (FF) derivatives, represent a promising class of materials for such electronics due to their inherent biodegradability and ease of hybridization with functional materials. However, the integration of ionic species with these peptides is often limited by the disruption of non-covalent interactions between FF derivatives. In this study, we developed biodegradable, ionic thermoelectric composites by co-assembling Fmoc-FF with deep eutectic solvents (DESs) composed of choline chloride (ChCl) and ethylene glycol (EG). Spectroscopic analyses revealed that Fmoc-FF formed eutectogels through π-π interactions between Fmoc groups, resulting in a highly porous colloidal network. The Fmoc-FF eutectogels exhibited an ionic conductivity of up to 47.5 mS·cm−1 and a Seebeck coefficient of 7.39 mV·K−1, making them suitable for heat harvesting. Additionally, they were entirely degraded within 48 h under proteolytic conditions, confirming their biodegradability. The eutectogels also displayed self-healing and shear-thinning behaviors, highlighting compatibility with additive manufacturing techniques for device integration.Graphical

Magnetically Driven Self-Degrading Zinc-Containing Cystine Microrobots for Treatment of Prostate Cancer.

Prostate cancer is the most commonly diagnosed tumor disease in men, and its treatment is still a big challenge in standard oncology therapy. Magnetically actuated microrobots represent the most promising technology in modern nanomedicine, offering the advantage of wireless guidance, effective cell penetration, and non-invasive actuation. Here, new biodegradable magnetically actuated zinc/cystine-based microrobots for in situ treatment of prostate cancer cells are reported. The microrobots are fabricated via metal-ion-mediated self-assembly of the amino acid cystine encapsulating superparamagnetic Fe3 O4 nanoparticles (NPs) during the synthesis, which allows their precise manipulation by a rotating magnetic field. Inside the cells, the typical enzymatic reducing environment favors the disassembly of the aminoacidic chemical structure due to the cleavage of cystine disulfide bonds and disruption of non-covalent interactions with the metal ions, as demonstrated by in vitro experiments with reduced nicotinamide adenine dinucleotide (NADH). In this way, the cystine microrobots served for site-specific delivery of Zn2+ ions responsible for tumor cell killing via a "Trojan horse effect". This work presents a new concept of cell internalization exploiting robotic systems' self-degradation, proposing a step forward in non-invasive cancer therapy.

Insights into changes in binding affinity caused by disease mutations in protein-protein complexes

Mutation of amino acid residues at protein-protein interfaces alters the binding affinity of protein-protein complexes and may lead to diseases. In this study, we have systematically analysed the relationship between the changes in binding affinity upon amino acid substitutions and the effect of mutations as disease-causing or neutral. We observed that a large proportion of disease-causing mutations decrease the binding affinity in all the considered datasets such as (i) experimentally known binding affinity and disease causing mutations, (ii) experimentally known binding affinity and predicted effects of mutations, and (iii) experimentally known disease causing mutations and predicted binding affinity. However, this relationship depends on the disease class, and the statistics indicate that factors other than binding affinity are also influencing the disease development. Further, structural analysis of protein-protein complexes revealed that disease-causing mutations are mainly attributed with the disruption of non-covalent interactions. In certain cancers, several mutations increase the binding affinity and they may have been selected to enhance cell survival and growth. Further, incorporating the effects of mutations on binding affinity in protein-protein interaction network studies may enable researchers to deduce the mechanisms of specific diseases and also help to identify novel drug targets.

Enhancing the Carboxylation Efficiency of Silk Fibroin through the Disruption of Noncovalent Interactions.

Silk fibroin is a semicrystalline protein used as a renewable polymer source and as a biomaterial platform, but existing methods to synthetically modify fibroin suffer from low efficiencies that can limit the protein's utility. This work reports on a mild synthesis that results in a 2-fold increase in carboxylation through the disruption of noncovalent interactions during the reaction. Importantly, silk fibroin maintains its ability to form β-sheets that are critical for tailoring mechanical and degradation properties, as well as for rendering solid constructs (e.g., films and scaffolds) insoluble in water. Increasing carboxyl functionalization affords control over protein charge, which permits tailoring the loading and release of small molecules using electrostatic interactions. Disruption of noncovalent interactions during aqueous carbodiimide coupling also significantly enhances conjugation efficiency of molecules containing primary amine groups, thus enabling high degrees of functionalization with biological molecules, such as proteins and peptides, for biomaterial applications.

Radical solutions: Principles and application of electron-based dissociation in mass spectrometry-based analysis of protein structure.

In recent years, electron capture (ECD) and electron transfer dissociation (ETD) have emerged as two of the most useful methods in mass spectrometry-based protein analysis, evidenced by a considerable and growing body of literature. In large part, the interest in these methods is due to their ability to induce backbone fragmentation with very little disruption of noncovalent interactions which allows inference of information regarding higher order structure from the observed fragmentation behavior. Here, we review the evolution of electron-based dissociation methods, and pay particular attention to their application in "native" mass spectrometry, their mechanism, determinants of fragmentation behavior, and recent developments in available instrumentation. Although we focus on the two most widely used methods-ECD and ETD-we also discuss the use of other ion/electron, ion/ion, and ion/neutral fragmentation methods, useful for interrogation of a range of classes of biomolecules in positive- and negative-ion mode, and speculate about how this exciting field might evolve in the coming years.

Self-Association of Organic Acids in Petroleum and Canadian Bitumen Characterized by Low- and High-Resolution Mass Spectrometry

We examine solution-phase aggregation for a whole crude oil, whole bitumen, and bitumen distillate fractions by negative-ion electrospray ionization [(−) ESI] detected by both high-resolution [Fourier transform ion cyclotron resonance (FT-ICR)] and low-resolution [linear quadrupole ion trap (LTQ)] mass spectrometry (MS). Aggregate formation for both crude oil and bitumens is concentration-dependent. At high concentrations (i.e., >1 mg/mL), the disruption of noncovalent interactions between heteromultimers by low-energy collision-activated dissociation (CAD) yields LTQ dissociation mass spectra with molecular-weight distributions identical to those observed by FT-ICR MS analysis at lower concentrations for purely monomeric species. These materials can exist as aggregates in solution even at high dilution (less than 0.1 mg/mL). We demonstrate the concentration and boiling point dependence for multimerization of polar acidic species in the Athabasca bitumen and bitumen distillates. Interestingly, the lowest boiling distillation cut (375−400 °C) displays the highest aggregation tendency, with dimers at concentrations as low as 0.05 mg/mL. Higher boiling point distillation cuts display a decreased aggregation tendency with an increasing cut point. High-resolution negative-ESI FT-ICR MS of the bitumen distillation fractions reveals the elemental composition, and thus the class, type, and carbon number of the multimeric species. Acidic heteroatomic classes for the distillation cut multimers include O4, S1O4, O3, S1O3, N1O2, and N1S1O2. The most abundant multimers for the 375−400 °C distillation cut are O4 species, whereas the 450−475 °C cut contains N1O2 multimers in the highest relative abundance. Changes in multimer heteroatom content as a function of the monomer composition and distillation cut suggest that aggregation depends upon the chemical functionalities of the monomer species.

Structural Requirements for the Interaction of Human IgA with the Human Polymeric Ig Receptor

Transport of polymeric IgA onto mucosal surfaces to become secretory IgA is mediated by the polymeric Ig receptor (pIgR). To study the interaction of human dimeric IgA (dIgA) (the predominant form of IgA polymer) with the human pIgR (hpIgR), we generated recombinant wild-type dIgA1 and dIgA2m(1) and various mutant dIgA1 and analyzed their interaction with a recombinant human secretory component and membrane-expressed hpIgR. We found that wild-type dIgA1 and dIgA2m(1) bound to recombinant human secretory component with similar affinity and were transcytosed by the hpIgR to the same extent. Mutation of the IgA Calpha2 domain residue Cys311 to Ser reduced binding to hpIgR, possibly through disruption of noncovalent interactions between the Calpha2 domain and domain 5 of the receptor. Within the Calpha3 domain of IgA1, we found that combined mutation of residues Phe411, Val413, and Thr414, which lie close to residues previously implicated in hpIgR binding, abolished interaction with the receptor. Mutation of residue Lys377, located very close to this same region, perturbed receptor interaction. In addition, 4 aa (Pro440-Phe443), which lie on a loop at the domain interface and form part of the binding site for human FcalphaRI, appear to contribute to hpIgR binding. Lastly, use of a monomeric IgA1 mutant lacking the tailpiece revealed that the tailpiece does not occlude hpIgR-binding residues in IgA1 monomers. This directed mutagenesis approach has thus identified motifs lying principally across the upper surface of the Calpha3 domain (i.e., that closest to Calpha2) critical for human pIgR binding and transcytosis.

Effects of Water and Molecular Hydrogen on Heat Treatment of Turkish Low-Rank Coals

Two low-rank Turkish coals, Tuncbilek (TB) subbituminous and Goynuk (GN) lignite, were subjected to low-severity heat treatment with or without added water, under N2 or H2 atmospheres at 285−330 °C, both as original coals and after demineralization with HCl(aq)/HF(aq) treatment. The samples processed in H2−H2O combination seemed to be more dissociated or decomposed than those processed in N2−H2O or under H2 without water. Gas analyses and spectroscopy of samples clearly indicated an effect of water in enhancing decarboxylation reactions and that oxygen rejection from the coals was mainly due to CO2 formation. Water also enhanced the cleavage of aryl−ether bonds. These cleavage reactions are more pronounced in GN coal than in TB coal, probably due to a higher concentration of activated ether structures in the former coal. The disruption of noncovalent interactions is considered mainly responsible for the extensive depolymerization of TB coal. The role of H2 in these heat treatment conditions is considered ...