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2.
Nat Commun ; 14(1): 8136, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065938

RESUMO

Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F2α and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs.


Assuntos
Carboprosta , Dinoprosta , Receptores de Prostaglandina , Feminino , Humanos , Carboprosta/farmacologia , Dinoprosta/farmacologia , Latanoprosta , Ligantes , Receptores de Prostaglandina/agonistas , Receptores de Prostaglandina/química , Microscopia Crioeletrônica
3.
RSC Adv ; 12(46): 30024-30029, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36321105

RESUMO

A label-free aptasensor has been fabricated in order to detect adenosine triphosphate (ATP) using turn-on fluorescence DNA-Ag NCs. The fluorescence of the DNA-Ag NCs could increase remarkably with the addition of ATP mainly because ATP specifically interacts with its aptamer to change the microenvironment of the darkish DNA-Ag NCs located at one terminus or two termini due to the conformational alteration of the aptamer structure. The proposed sensor can detect ATP in a linear range of 6-27 mM with a good detection limit of 5.0 µM. Additionally, the proposed method succeeded in detecting ATP in fetal bovine serum.

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