Discovery of a single-subunit oligosaccharyltransferase that enables glycosylation of full-length IgG antibodies in .

Human immunoglobulin G (IgG) antibodies are one of the most important classes of biotherapeutic agents and undergo glycosylation at the conserved N297 site in the C2 domain, which is critical for IgG Fc effector functions and anti-inflammatory activity. Hence, technologies for producing authentically glycosylated IgGs are in high demand. While attempts to engineer for this purpose have been described, they have met limited success due in part to the lack of available oligosaccharyltransferase (OST) enzymes that can install linked glycans within the QYNST sequon of the IgG C2 domain.

Exposure to polyethylene microplastics exacerbate inflammatory bowel disease tightly associated with intestinal gut microflora.

Polyethylene microplastics (PE MPs) have sparked widespread concern about their possible health implications because of their abundance, pervasiveness in the environment and in our daily life. Multiple investigations have shown that a high dosage of PE MPs may adversely impact gastrointestinal health. In tandem with the rising prevalence of Inflammatory bowel disease (IBD) in recent decades, global plastic manufacturing has risen to more than 300 million tons per year, resulting in a build-up of plastic by-products such as PE MPs in our surroundings.

Bioreversible Anionic Cloaking Enables Intracellular Protein Delivery with Ionizable Lipid Nanoparticles.

Protein-based therapeutics comprise a rapidly growing subset of pharmaceuticals, but enabling their delivery into cells for intracellular applications has been a longstanding challenge. To overcome the delivery barrier, we explored a reversible, bioconjugation-based approach to modify the surface charge of protein cargos with an anionic "cloak" to facilitate electrostatic complexation and delivery with lipid nanoparticle (LNP) formulations. We demonstrate that the conjugation of lysine-reactive sulfonated compounds can allow for the delivery of various protein cargos using FDA-approved LNP formulations of the ionizable cationic lipid DLin-MC3-DMA (MC3).

Insights into the Binding Interactions between Microplastics and Human α-Synuclein Protein by Multispectroscopic Investigations and Amyloidogenic Oligomer Formation.

Aggregation of human α-synuclein protein is regarded to be a key stage in the etiology of Parkinson's disease and numerous other neurodegenerative illnesses. Microplastics pollution can be a potential agent to promote various neurodegenerative disorders. In this study, we have employed various multispectroscopic analytical methods to investigate the binding interactions between polyethylene (PE-MPs), polyvinyl chloride (PVC-MPs), polystyrene (PS-MPs) microplastics, and human α-synuclein protein.

Investigating the preferential interaction between imatinib mesylate and VEGF G-quadruplex DNA as therapeutic strategies for cancer treatment: Biophysical and molecular modelling approaches.

G-Quadruplex DNA (GQ-DNA) is one of the most important non-canonical nucleic acid structures. GQ-DNA forming sequences are present in different crucial genomic regions and are abundant in promoter regions of several oncogenes. Therefore, GQ-DNA is an important target for anticancer drugs and hence binding interactions between GQ-DNA and small molecule ligands are of great importance.

Revealing the Improved Binding Interaction of Plant Alkaloid Harmaline with Human Hemoglobin in Molecular Crowding Condition.

Harmaline and harmine are two structurally similar β-carboline alkaloids with several therapeutic activities, such as anti-inflammatory, antioxidant, neuroprotective, nephroprotective, antidiabetic, and antitumor activities. It has been previously reported that the interaction between harmaline and hemoglobin (Hb) is weak in buffer media compared to harmine. Crowding agents induce a molecular crowding environment in the condition, which is almost similar to the intracellular environment.

Quercetin Exhibits Preferential Binding Interaction by Selectively Targeting HRAS1 I-Motif DNA-Forming Promoter Sequences.

I-Motif (iM) DNA structures represent among the most significant noncanonical nucleic acid configurations. iM-forming DNA sequences are found in an array of vital genomic locations and are particularly frequent in the promoter islands of various oncogenes. Thus, iM DNA is a crucial candidate for anticancer medicines; therefore, binding interactions between iM DNA and small molecular ligands, such as flavonoids, are critically important.

Tuning light-driven oxidation of styrene inside water-soluble nanocages.

Selective functionalization of innate sp C-H bonds under ambient conditions is a grand synthetic challenge in organic chemistry. Here we combine host-guest charge transfer-based photoredox chemistry with supramolecular nano-confinement to achieve selective carbonylation of styrene by tuning the dioxygen concentration. We observe exclusive photocatalytic formation of benzaldehyde under excess O (>1 atm) while Markovnikov addition of water produced acetophenone in deoxygenated condition upon photoexcitation of confined styrene molecules inside a water-soluble cationic nanocage.

Multispectroscopic Investigations of the Binding Interaction between Polyethylene Microplastics and Human Hemoglobin.

In this investigation, different multispectroscopic analytical techniques have been used to explore the interaction between polyethylene microplastics (PE-MPs) and human hemoglobin (HHb), an oxygen carrier in the human blood circulatory system. Ultraviolet-visible absorption studies have demonstrated that HHb molecules may interact with PE-MPs, and thermal melting studies have indicated that PE-MPs have a stabilizing effect on HHb. Further circular dichroism and Fourier transform infrared spectroscopic studies have revealed the distinct changes in HHb's secondary structures caused by the formation of the HHb-PE-MP binding complex.

Exploring the Structural Importance of the C3=C4 Double Bond in Plant Alkaloids Harmine and Harmaline on Their Binding Interactions with Hemoglobin.

Harmine and harmaline are two structurally similar heterocyclic β-carboline plant alkaloids with various therapeutic properties, having a slight structural difference in the C3=C4 double bond. In the present study, we have reported the nature of the interaction between hemoglobin (Hb) with harmine and harmaline by employing several multispectroscopic, calorimetric, and molecular docking approaches. Fluorescence spectroscopic studies have shown stronger interaction of harmine with Hb compared to that of almost structurally similar harmaline.

Uncovering the Contrasting Binding Behavior of Plant Flavonoids Fisetin and Morin Having Subsidiary Hydroxyl Groups (-OH) with HRAS1 and HRAS2 i-Motif DNA Structures: Decoding the Structural Alterations and Positional Influences.

Research on the interactions of naturally existing flavonoids with various noncanonical DNA such as i-motif (IM) DNA structures is helpful in comprehending the molecular basis of binding mode as well as providing future direction for the application and invention of novel effective therapeutic drugs. IM DNA structures have been identified as prospective anticancer therapeutic targets, and flavonoids are smaller molecules with a variety of health-promoting attributes, including anticancer activities. The extensive investigation comprising a series of techniques reveals the contrasting mode of the binding behavior of fisetin and morin with various IM DNA structures.

Unravelling the Drug Encapsulation Ability of Functional DNA Origami Nanostructures: Current Understanding and Future Prospects on Targeted Drug Delivery.

Rapid breakthroughs in nucleic acid nanotechnology have always driven the creation of nano-assemblies with programmable design, potent functionality, good biocompatibility, and remarkable biosafety during the last few decades. Researchers are constantly looking for more powerful techniques that provide enhanced accuracy with greater resolution. The self-assembly of rationally designed nanostructures is now possible because of bottom-up structural nucleic acid (DNA and RNA) nanotechnology, notably DNA origami.

Predictive Platforms of Bond Cleavage and Drug Release Kinetics for Macromolecule-Drug Conjugates.

Macromolecule-drug conjugates (MDCs) occupy a critical niche in modern pharmaceuticals that deals with the assembly and combination of a macromolecular carrier, a drug cargo, and a linker toward the creation of effective therapeutics. Macromolecular carriers such as synthetic biocompatible polymers and proteins are often exploited for their inherent ability to improve drug circulation, prevent off-target drug cytotoxicity, and widen the therapeutic index of drugs. One of the most significant challenges in MDC design involves tuning their drug release kinetics to achieve high spatiotemporal precision.