Cutting-edge Bioinformatics strategies for synthesizing Cyclotriazadisulfonamide (CADA) analogs in next-Generation HIV therapies.

Cyclotriazadisulfonamide (CADA) is a macrocyclic compound known for its unique mechanism in inhibiting HIV infection by downregulating the CD4 T-cell receptor, a crucial entry point for the virus. Unlike other antiretrovirals, CADA exhibits activity against a wide range of HIV strains, as all HIV variants require CD4 binding for infection. Furthermore, CADA has shown a synergistic effect with clinically approved anti-HIV drugs, offering potential for enhanced therapeutic strategies (Vermeire & Schols, [65]).

Establishment of a graphene quantum dot (GQD) based steroid binding assay for the nuclear progesterone receptor (pgr).

Previously, we established a homogeneous assay for membrane progesterone receptor alpha (mPRα) ligands by conjugating semiconductor nanoparticles known as graphene quantum dots (GQDs) to mPRα. When mixed with a progesterone-BSA-fluorescein isothiocyanate conjugate (P4-BSA-FITC), fluorescence occurred by fluorescence resonance energy transfer (FRET) but was reduced by the ligand-receptor binding activity. The established way showed ligand specificity as mPRα protein.

Zebrafish prss59.1 is involved in chorion development.

The prss59.1 gene was identified as one of 11 genes that were highly upregulated during the induction of ovulation in zebrafish by using an in vivo ovulation assay. Previously, we conducted biochemical characterization of Prss59.

The antagonistic activity of extracts on mPRα.

The current study attempted to evaluate the antagonistic activity of compounds isolated and purified from the marine algae during cultivation. The compounds were collected on a filter, concentrated on ODS columns and separated by HPLC. Two peaks that showed competitive progesterone binding activity with membrane progesterone receptor α (mPRα) were purified.

Purification and Identification of the 20S Proteasome Complex from Zebrafish.

The proteasome is a large polymeric protease complex responsible for degradation of intracellular proteins and generation of peptides. In this study, we purified a native 20S proteasome protein complex from zebrafish () from the whole body. The cytosolic fraction of zebrafish hydrolyzed Suc-Leu-Leu-Val-Tyr-MCA (Suc-LLVY-MCA), a well-known substrate for the proteasome, in the presence of sodium dodecyl sulfate.

Establishment of a steroid binding assay for membrane progesterone receptor alpha (PAQR7) by using graphene quantum dots (GQDs).

Currently, semiconductor nanoparticles known as quantum dots (QDs) have attracted interest in various application fields such as those requiring sensing properties, binding assays, and cellular imaging and are the very important in the acceleration of drug discovery due to their unique photophysical properties. Here, we applied graphene quantum dots (GQDs) for the binding assay of membrane progesterone receptor alpha (mPRα), one of the probable membrane receptors that have potential in drug discovery applications. By coupling the amino groups of mPRα with GQDs, we prepared fluorogenic GQD-conjugated mPRα (GQD-mPRα).

Pax2a is expressed in oocytes and is responsible for early development and oogenesis in zebrafish.

Eleven genes, including pax2a, were selected as candidate ovulation-inducing genes on the basis of microarray analysis and RNA sequencing in our previous study. The purpose of this study was to investigate the role of the pax2a gene in the ovulation-inducing process. F2 pax2a homozygous mutant zebrafish possessing a deletion of 6 nucleotides were established in this study.

Two-Step Mechanism of Cyclin B Degradation Initiated by Proteolytic Cleavage with the 26 S Proteasome in Fish.

To complete meiosis II, cyclin B is degraded in a short period by the inactivation of M-phase promoting factor (MPF). Previously, we showed that the destruction of cyclin B was initiated by the ubiquitin-independent proteolytic activity of the 26 S proteasome through an initial cut in the N-terminus of cyclin (at K57 in the case of goldfish cyclin B). We hypothesized that this cut allows cyclin to be ubiquitinated for further destruction by the ubiquitin-dependent proteolytic pathway, which leads to MPF inactivation.