bioconjugate

Introducing glycans represents an efficient chemical approach to improve the pharmacological properties of therapeutic biomolecules. Herein, we report an efficient synthesis of glycoconjugates through chlorooxime-thiol conjugation. The reactive glycosyl chlorooximes, derived from pyranoses or furanoses, readily couple to a wide range of thiol-containing substrates, including peptides, sugars, and thiophenols. This method features mild reaction conditions and fast kinetics. Capability for aqueous media and gram-scale synthesis demonstrates the potential of this method in the bioconjugation of saccharides with biologically active molecules...

RNA ligands of retinoic acid-inducible gene I (RIG-I) are a promising class of oligonucleotide therapeutic with broad potential as antiviral agents, vaccine adjuvants, and cancer immunotherapies. However, their translation has been limited by major drug delivery barriers, including poor cellular uptake, nuclease degradation, and an inability to access the cytosol where RIG-I is localized. Here we address this challenge by engineering nanoparticles that harness covalent conjugation of 5'-triphospate RNA (3pRNA) to endosome-destabilizing polymers...

The delivery of proteins into the cytosol holds great promise for cell signaling manipulation and the development of precision medicine. However, this potency is challenged by achieving targeted and controlled delivery, specifically within diseased cells. In this study, we introduce a versatile and effective method for the precision delivery of therapeutic proteins to cancer cells by designing polyphenol-assisted biomineralization of zeolite imidazole framework-8 (ZIF-8). We demonstrate that by leveraging the strong noncovalent binding affinity of epigallocatechin gallate (EGCG) with both proteins and ZIF-8, our approach significantly enhances the biomineralization of ZIF-8, which in turn improves the efficiency of protein encapsulation and intracellular delivery...

Radiolabeling of biomolecules and cells with radiolabeled prosthetic groups has significant implications for nuclear medicine, imaging, and radiotherapy. Achieving site-specific and controlled incorporation of radiolabeled prostheses under mild reaction conditions is crucial for minimizing the impact on the bioactivity of the radiolabeled compounds. The targeting of natural and abundant amino acids during radiolabeling of biomolecules often results in nonspecific and uncontrolled modifications. Cysteine is distinguished by its low natural abundance and unique nucleophilicity...

In this work, the electrochemical behavior of 4-phenylurazole (Ph-Ur) was studied and the latter was used as a molecular anchor for the electrochemical bioconjugation of tyrosine (Y). Cyclic voltammetry (CV) and controlled potential coulometry (CPC) allowed the in-situ generation of the PTAD (4-phenyl-3 H-1,2,4-triazole-3,5(4 H)-dione) species from phenylurazole on demand for tyrosine electrolabeling. The chemoselectivity of the reaction was studied with another amino acid (lysine, Lys) and no changes in Lys were observed...

Asparaginyl ligases have been extensively utilized as valuable tools for site-specific bioconjugation or surface-modification. However, the application is hindered by the laborious and poorly reproducible preparation processes, unstable activity and ambiguous substrate requirements. To address these limitations, this study employed a structure-based rational approach to obtain a high-yield and high-activity protein ligase called OaAEP1-C247A-aa55-351. It was observed that OaAEP1-C247A-aa55-351 exhibits appreciable catalytic activities across a wide pH range, and the addition of the Fe3+ metal ion effectively enhances the catalytic power...

The exploration of pharmaceutically active agents and positron emission tomography (PET) tracers targeting CXCR4 has been a focal point in cancer research given its pivotal role in the development and progression of various cancers. While significant strides have been made in PET imaging with radiometal-labeled tracers, the landscape of 18 F-labeled small molecule tracers remains relatively limited. Herein, we introduce a novel and promising derivative, [18 F]SFB-AMD3465, as a targeted PET tracer for CXCR4...

A carboranylporphyrin of A3 B-type bearing a single pentafluorophenyl ring was prepared through the regioselective nucleophilic aromatic substitution reaction of the p -fluorine atoms in 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin with 9-mercapto- m -carborane. The reaction of this porphyrin with sodium azide led to the selective substitution of the p -fluorine atom in the pentafluorophenyl substituent with an azide functionality which upon reduction with SnCl2 resulted in the formation of the corresponding porphyrin with an amino group...

[This corrects the article DOI: 10.1039/D4RA00437J.].

Addressing the complex challenge of healing of bacterially infected wounds, this study explores the potential of lipid nanomaterials, particularly advanced ultradeformable particles (UDPs), to actively influence the wound microenvironment. The research introduces a novel therapeutic approach utilizing silver sulfadiazine (SSD) coupled with vitamin E (VE) delivered through UDPs (ethosomes/transferosomes/transethosomes). Comparative physicochemical characterization of these nanosized drug carriers reveals the superior stability of transethosomes, boasting a zeta potential of -36...

INTRODUCTION: Doxorubicin (DOX) emerges as a cornerstone in the arsenal of potent chemotherapeutic agents. Yet, the clinical deployment of DOX is tarnished by its proclivity to induce severe cardiotoxic effects, culminating in heart failure and other consequential morbidities. In response, a panoply of strategies has undergone rigorous exploration over recent decades, all aimed at attenuating DOX's cardiotoxic impact. The advent of encapsulating DOX within lipidic or polymeric nanocarriers has yielded a dual triumph, augmenting DOX's therapeutic efficacy while mitigating its deleterious side effects...

No abstract text is available yet for this article.

89 Zr-immunoPET is a hot topic as 89 Zr cumulates the advantages of 64 Cu and 124 I without their drawbacks. We report the synthesis of a model ligand of a chiral bioconjugable tetrahydroxamic chelator combining the desferriferrioxamine B siderophore and 1-hydroxy-2-piperidone ((PIPO)H), a chiral cyclic hydroxamic acid derivative, and the study by NMR spectroscopy of its zirconium complex. Nuclear Overhauser effect measurements (ROESY) indicated that the complex exists in the form of two diastereomers, in 77 : 23 ratio, resulting from the combination of the central chiralities at the 3-C of the (PIPO)H component and at the Zr4+ cation...

Pain affects one-third of the global population and is a significant public health issue. The use of opioid drugs, which are the strongest painkillers, is associated with several side effects, such as tolerance, addiction, overdose, and even death. An increasing demand for novel, safer analgesic agents is a driving force for exploring natural sources of bioactive peptides with antinociceptive activity. Since the G protein-coupled receptors (GPCRs) play a crucial role in pain modulation, the discovery of new peptide ligands for GPCRs is a significant challenge for novel drug development...

Penicillium digitatum is the causal agent of green mold, a primary postharvest disease of citrus fruits. This study evaluated the efficacy of a novel photoactive chitosan-riboflavin bioconjugate (CH-RF) to control green mold in vitro and in lemon fruit. The results showed total inhibition of P. digitatum growth on APDA supplemented with CH-RF at 0.5% ( w / v ) and a significant reduction of 84.8% at 0.25% ( w / v ). Lemons treated with CH-RF and kept under controlled conditions (20 °C and 90-95% relative humidity) exhibited a noteworthy reduction in green mold incidence four days post-inoculation...

Nucleic acids in the form of siRNA, antisense oligonucleotides or mRNA are currently explored as new promising modalities in the pharmaceutical industry. Particularly, the success of mRNA-vaccines against SARS-CoV-2, along with the successful development of the first sugar-modified siRNA therapeutics has inspired the field. The development of nucleic acid therapeutics requires efficient chemistry to link oligonucleotides to chemical structures that can improve stability, boost cellular uptake, or enable specific targeting...

Lung cancer is a major cause of death worldwide, being often detected at a later stage due to the non-appearance of early symptoms. Therefore, specificity of the treatment is of utmost importance for its effective treatment. Precision medicine is a personalized therapy based on the genomics of the patient to design a suitable drug approach. Genetic mutations render the tumor resistant to specific mutations and the therapy is in vain even though correct medications are prescribed. Therefore, Precision medicine needs to be explored for the treatment of Non-small cell lung cancer (NSCLC)...

Enhancing the accumulation and retention of small-molecule probes in tumors is an important way to achieve accurate cancer diagnosis and therapy. Enzyme-stimulated macrocyclization of small molecules possesses great potential for enhanced positron emission tomography (PET) imaging of tumors. Herein, we reported an 18 F-labeled radiotracer [18 F]AlF-RSM for legumain detection in vivo. The tracer was prepared by a one-step aluminum-fluoride-restrained complexing agent ([18 F]AlF-RESCA) method with high radiochemical yield (RCY) (88...

Cyclen-peptide bioconjugates are usually prepared in multiple steps that require individual preparation and purification of the cyclic peptide and hydrophilic cyclen derivatives. An efficient strategy is discovered for peptide cyclization and functionalization toward lanthanide probe via three components intermolecular crosslinking on solid-phase peptide synthesis with high conversion yield. Multifunctionality can be conferred by introducing different modular parts or/and metal ions on the cyclen-embedded cyclopeptide...

Disorder of complement response is a significant pathogenic factor causing some autoimmune and inflammation diseases. The Ornithodoros moubata Complement Inhibitor (OmCI), a small 17 kDa natural protein, was initially extracted from soft tick salivary glands. The protein was found binding to complement C5 specifically, inhibiting the activation of the complement pathway, which is a successful therapeutic basis of complement-mediated diseases. However, a short half-life due to rapid renal clearance is a common limitation of small proteins for clinical application...