The hemolymph protein HP19 of the rice moth, Corcyra cephalonica, mediates the 20-hydroxyecdysone (20E)-dependent acid phosphatase (ACP) activity at a nongenomic level. Affinity-purified polyclonal antibody against HP19 (alphaHP19-IgG) was used in the present study to understand the role of HP19 during the postembryonic development of Corcyra. In the in vitro studies, HP19 action was blocked either by immuno-precipitation using alphaHP19-IgG, prior to its addition to the fat body culture or by the addition of the antibody directly to the culture, along with 20E and hemolymph containing HP19. The alphaHP19-IgG blocked the HP19-mediated 20E-dependent ACP activation. In the in vivo studies, the alphaHP19-IgG was injected into the fully developed last (final/Vth) instar larvae of Corcyra, to complex the HP19 in vivo, in order to block the action of HP19. The injection of alphaHP19-IgG resulted in defective development of larvae, which grew either into non-viable larvae or larval-pupal/pupal-adult intermediates relative to the effect of pre-immune IgG injected controls. The present study shows that HP19 plays an important role in controlling the metamorphosis of Corcyra by regulating the 20E-dependent ACP activity. Coupled with the earlier findings, the ecdysteroid hormone regulates this action at a nongenomic level.
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ACS Pharmacol Transl Sci
May 2024
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 751 23, Sweden.
Affibody-mediated PNA-based pretargeting shows promise for HER2-expressing tumor radiotherapy. In our recent study, a 15-mer Z-HP15 affibody-PNA conjugate, in combination with a shorter 9-mer [Lu]Lu-HP16 effector probe, emerged as the most effective pretargeting strategy. It offered a superior tumor-to-kidney uptake ratio and more efficient tumor targeting compared to longer radiolabeled effector probes containing 12 or 15 complementary PNA bases.
View Article and Find Full Text PDFJ Med Chem
December 2022
Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China.
Selective glucocorticoid receptor modulators (SGRMs), which can dissociate the transactivation from the transrepression of the glucocorticoid receptor (GR), are regarded as very promising therapeutics for inflammatory and autoimmune diseases. We previously discovered a SGRM based on the passive antagonistic conformation of GR and bioassays. In this study, we further analyzed the dynamic changes of the passive antagonistic state upon the binding of and designed and synthesized 62 -acyl-6-sulfonamide-tetrahydroquinoline derivatives by structural optimization of .
View Article and Find Full Text PDFOrg Biomol Chem
August 2022
School of Chemistry and Forensics, University of Kent, Canterbury, Kent, CT2 7NH, UK.
Supramolecular self-associating amphiphiles are a class of amphiphilic salt, the anionic component of which is 'frustrated' in nature, meaning multiple hydrogen bonding modes can be accessed simultaneously. Here we derive critical micelle concentration values for four supramolecular self-associating amphiphiles using the standard pendant drop approach and present a new high-throughput, optical density measurement based methodology, to enable the estimation of critical micelle concentrations over multiple temperatures. In addition, we characterise the low-level hydrogen bonded self-association events in the solid state, through single crystal X-ray diffraction, and in polar organic DMSO- solutions using a combination of H NMR techniques.
View Article and Find Full Text PDFVaccines (Basel)
December 2021
State Key Laboratory of Pathogen and Biosecurity, Institute of Biotechnology, Academy of Military Medical Sciences, 20 Dongda Street, Fengtai District, Beijng 100071, China.
(), heat-shock protein A (HspA), is a bacterial heat-shock chaperone that serves as a nickel ion scavenging protein. Ni is an important co-factor required for the maturation and enzymatic activity of urease and [NiFe] hydrogenase, both of which are key virulence factors for pathogen survival and colonization. HspA is an important target molecule for the diagnosis, treatment, and immune prevention of .
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2022
Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Binding of different ligands to glucocorticoid receptor (GR) may induce different conformational changes and even trigger completely opposite biological functions. To understand the allosteric communication within the GR ligand binding domain, the folding pathway of helix 12 (H12) induced by the binding of the agonist dexamethasone (DEX), antagonist RU486, and modulator AZD9567 are explored by molecular dynamics simulations and Markov state model analysis. The ligands can regulate the volume of the activation function-2 through the residues Phe737 and Gln738.
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