000125957 001__ 125957
000125957 005__ 20241125101134.0
000125957 0247_ $$2doi$$a10.1002/chem.202203841
000125957 0248_ $$2sideral$$a133565
000125957 037__ $$aART-2023-133565
000125957 041__ $$aeng
000125957 100__ $$aClemente, Francesca
000125957 245__ $$aLight-triggered control of Glucocerebrosidase inhibitors: towards photoswitchable pharmacological Chaperones
000125957 260__ $$c2023
000125957 5060_ $$aAccess copy available to the general public$$fUnrestricted
000125957 5203_ $$aPiperidine-based photoswitchable derivatives have been developed as putative pharmacological chaperones for glucocerebrosidase (GCase), the defective enzyme in Gaucher disease (GD). The structure-activity study revealed that both the iminosugar and the light-sensitive azobenzene are essential features to exert inhibitory activity towards human GCase and a system with the correct inhibition trend (IC50 of the light-activated form lower than IC50 of the dark form) was identified. Kinetic analyses showed that all compounds are non-competitive inhibitors (mixed or pure) of GCase and the enzyme allosteric site involved in the interaction was identified by means of MD simulations. A moderate activity enhancement of mutant GCase assessed in GD patients' fibroblasts (ex vivo experiments) carrying the most common mutation was recorded. This promising observation paves the way for further studies to improve the benefit of the light-to-dark thermal conversion for chaperoning activity.
000125957 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E34-20R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-104090RB-100
000125957 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000125957 590__ $$a3.9$$b2023
000125957 592__ $$a1.058$$b2023
000125957 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b80 / 231 = 0.346$$c2023$$dQ2$$eT2
000125957 593__ $$aChemistry (miscellaneous)$$c2023$$dQ1
000125957 593__ $$aOrganic Chemistry$$c2023$$dQ1
000125957 593__ $$aCatalysis$$c2023$$dQ2
000125957 594__ $$a7.9$$b2023
000125957 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000125957 700__ $$aDavighi, Maria Giulia
000125957 700__ $$aMatassini, Camilla
000125957 700__ $$aCardona, Francesca
000125957 700__ $$aGoti, Andrea
000125957 700__ $$aMorrone, Amelia
000125957 700__ $$aPaoli, Paolo
000125957 700__ $$0(orcid)0000-0003-3433-6701$$aTejero, Tomás$$uUniversidad de Zaragoza
000125957 700__ $$0(orcid)0000-0002-2202-3460$$aMerino, Pedro$$uUniversidad de Zaragoza
000125957 700__ $$aCacciarini, Martina
000125957 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000125957 773__ $$g29, 19 (2023), e202203841 [12 pp.]$$pChemistry (Weinh.)$$tChemistry - A European Journal$$x0947-6539
000125957 8564_ $$s3721887$$uhttps://zaguan.unizar.es/record/125957/files/texto_completo.pdf$$yVersión publicada
000125957 8564_ $$s2596193$$uhttps://zaguan.unizar.es/record/125957/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000125957 909CO $$ooai:zaguan.unizar.es:125957$$particulos$$pdriver
000125957 951__ $$a2024-11-22-11:59:55
000125957 980__ $$aARTICLE