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Reengineering or the rational redesigning of the binding pocket of the Cellular Retinoic Acid Binding Protein II ( CRABPII) can easily copy the binding found in rhodopsin protein, hence giving rise to a mutant that can bind retinal as a protonated Schiff base. The all-trans-retinal bound to CRABPII triple mutant are found to have a high-resolution crystal structure, which then proves the formation of an imine between the retinal and the protein.

Research was conducted to examine intramolecular hydrogen bonding in chloroform in small polyamides. Variable temperature infrared and nuclear magnetic resonance spectroscopies were used in the study of specific hydrogen bonds in selected triamides in organic solvents. Results indicate that each of the nine triamides studied exhibited its own unique intramolecular hydrogen-bonding pattern and that not all of the model peptides prefer the intramolecular hydrogen-bonded conformation.

Abstract The study of the potential risks associated with the manufacture, use, and disposal of nanoscale materials, and their mechanisms of toxicity, is important for the continued advancement of nanotechnology. Currently, the most widely accepted paradigms of nanomaterial toxicity are oxidative stress and inflammation, but the underlying mechanisms are poorly defined. This review will highlight the significance of autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Most endocytic routes of nanomaterial cell uptake converge upon the lysosome, making the lysosomal compartment the most common intracellular site of nanoparticle sequestration and degradation. In addition to the endo-lysosomal pathway, recent evidence suggests that some nanomaterials can also induce autophagy. Among the many physiological functions, the lysosome, by way of the autophagy (macroautophagy) pathway, degrades intracellular pathogens, and damaged organelles and proteins. Thus, autophagy induction by nanoparticles may be an attempt to degrade what is perceived by the cell as foreign or aberrant. While the autophagy and endo-lysosomal pathways have the potential to influence the disposition of nanomaterials, there is also a growing body of literature suggesting that biopersistent nanomaterials can, in turn, negatively impact these pathways. Indeed, there is ample evidence that biopersistent nanomaterials can cause autophagy and lysosomal dysfunctions resulting in toxicological consequences.

Despite imaging agents being some of the earliest nanomedicines in clinical use, the vast majority of current research and translational activities in the nanomedicine field involves therapeutics, while imaging agents are severely underrepresented. The reasons for this lack of representation are several fold, including difficulties in synthesis and scale‐up, biocompatibility issues, lack of suitable tissue/disease selective targeting ligands and receptors, and a high bar for regulatory approval. The recent focus on immunotherapies and personalized medicine, and development of nanoparticle constructs with better tissue distribution and selectivity, provide new opportunities for nanomedicine imaging agent development. This manuscript will provide an overview of trends in imaging nanomedicine characterization and biocompatibility, and new horizons for future development. This article is categorized under:Diagnostic Tools > in vivo Nanodiagnostics and ImagingToxicology and Regulatory Issues in Nanomedicine > Toxicology of NanomaterialsToxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine [ABSTRACT FROM AUTHOR]

A study is conducted to report the rational redesign of cellular retionic acid binding protein II (CRABPII) into a retinal -protonated Schiff base (PSB)-forming protein to mimic rhodopsin. The cellular retionic acid binding protein site is redesigned to mimic the same binding mode found in rhodopsin.

The binding of retinoic acid to mutants of Cellular Retinoic Acid Binding Protein II (CRABPII) was evaluated to better understand the importance of the direct protein/ligand interactions. The important role of Arg111 for the correct structure and function of the protein was verified and other residues that directly affect retinoic acid binding have been identified. Furthermore, retinoic acid binding to CRABPII mutants that lack all previously identified interacting amino acids was rescued by providing a carboxylic acid dimer partner in the form of a Glu residue. Proteins 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The chloroquine family of antimalarials has a long history of use, spanning many decades. Despite this extensive clinical experience, novel applications, including use in autoimmune disorders, infectious disease, and cancer, have only recently been identified. While short term use of chloroquine or hydroxychloroquine is safe at traditional therapeutic doses in patients without predisposing conditions, administration of higher doses and for longer durations are associated with toxicity, including retinotoxicity. Additional liabilities of these medications include pharmacokinetic profiles that require extended dosing to achieve therapeutic tissue concentrations. To improve chloroquine therapy, researchers have turned toward nanomedicine reformulation of chloroquine and hydroxychloroquine to increase exposure of target tissues relative to off-target tissues, thereby improving the therapeutic index. This review highlights these reformulation efforts to date, identifying issues in experimental designs leading to ambiguity regarding the nanoformulation improvements and lack of thorough pharmacokinetics and safety evaluation. Gaps in our current understanding of these formulations, as well as recommendations for future formulation efforts, are presented. [ABSTRACT FROM AUTHOR]

Nanotechnology for drug delivery has made significant advancements over the last two decades. Innovations have been made in cancer research and development, including chemotherapies, imaging agents, and vaccine strategies, as well as other therapeutic areas, e.g., the recent commercialization of mRNA lipid nanoparticles as vaccines against the SARS-CoV-2 virus. The field has also seen technological advancements to aid in addressing the complex questions posed by these novel therapies. In this latest edition of protocols and methods for nanoparticle characterization, we highlight both old and new methodologies for defining physicochemical properties, present both in vitro and in vivo methods to test for a variety of immunotoxicities, and describe assays used for pharmacological studies to assess drug release and tissue distribution., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite imaging agents being some of the earliest nanomedicines in clinical use, the vast majority of current research and translational activities in the nanomedicine field involves therapeutics, while imaging agents are severely underrepresented. The reasons for this lack of representation are several fold, including difficulties in synthesis and scale-up, biocompatibility issues, lack of suitable tissue/disease selective targeting ligands and receptors, and a high bar for regulatory approval. The recent focus on immunotherapies and personalized medicine, and development of nanoparticle constructs with better tissue distribution and selectivity, provide new opportunities for nanomedicine imaging agent development. This manuscript will provide an overview of trends in imaging nanomedicine characterization and biocompatibility, and new horizons for future development. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine., (© 2020 Wiley Periodicals LLC.)

Continued advancements in nanotechnology are expanding the boundaries of medical research, most notably as drug delivery agents for treatment against cancer. Drug delivery with nanotechnology can offer greater control over the biodistribution of therapeutic agents to improve the therapeutic index. In the last 20 years, a number of nanomedicines have transitioned into the clinic. As nanomedicines evolve, techniques to properly evaluate their safety and efficacy must also evolve. Characterization methods for nano-based materials must be adapted to the demands of nanomedicine developers and regulators. This second edition book provides updated characterization protocols designed to address the clinical potential of nanomedicines during their preclinical development. In this chapter, the characterization challenges of nanoparticles intended for drug delivery will be discussed, along with examples of advancements and improvements in nanomedicine characterization.