A bivalent inhibitor against TDRD3 to suppress phase separation of methylated G3BP1.

The formation of membrane-less organelles is driven by multivalent weak interactions while mediation of such interactions by small molecules remains an unparalleled challenge. Here, we uncovered a bivalent inhibitor that blocked the recruitment of TDRD3 by the two methylated arginines of G3BP1. Relative to the monovalent inhibitor, this bivalent inhibitor demonstrated an enhanced binding affinity to TDRD3 and capability to suppress the phase separation of methylated G3BP1, TDRD3, and RNAs, and in turn inhibit the stress granule growth in cells.

Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.

The ankle-link complex (ALC) consists of USH2A, WHRN, PDZD7, and ADGRV1 and plays an important role in hair cell development. At present, its architectural organization and signaling role remain unclear. By establishing Adgrv1 Y6236fsX1 mutant mice as a model of the deafness-associated human Y6244fsX1 mutation, the authors show here that the Y6236fsX1 mutation disrupts the interaction between adhesion G protein-coupled receptor V subfamily member 1 (ADGRV1) and other ALC components, resulting in stereocilia disorganization and mechanoelectrical transduction (MET) deficits.

Palladium (II), platinum (II) and silver (I) complexes with oxazolines: Their synthesis, characterization, DFT calculation, molecular docking and antitumour effects.

Six new Pd(II), Pt(II) and Ag(I) complexes, (1);{Pd (L)]2CH}Cl} (2); Pt(L)(DMSO)Cl; 3; {PtL]CH}·PhCOO⋅11NO; 4; {[Pt(L)]CH}; the binuclear cyclometalated complex the polymer chain (5); {[PtL]CH}·NO}; and the polymeric silver species (6); Zn(L)·AgNO·CHCl were synthesized and thoroughly characterized using X-ray diffraction and spectroscopic techniques (L=(S,S)-1,4-i-PrOx]CH}Cl, L=Di(2,2-bis(4R-isopropyl-4,5-dihydro-oxazol-2-yl)acetonitrile) zinc (II) (B);L= 1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)benzene (A); L= 1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)benzene，L=1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)-benzene，L=Di(2,2-bis(4S-isopropyl-4,5-dihydrooxazol-2-yl)acetonitrile) zinc (II). Complexes 1-6 showed cytotoxic effects against human tumour cell lines, including a multidrug-resistant subline. Oxazoline and Pd complex 1 induced apoptosis in A549 cells.