رسالة جامعية
Development and applications of photoswitchable ligands for G protein-coupled receptors
| العنوان: | Development and applications of photoswitchable ligands for G protein-coupled receptors |
|---|---|
| المؤلفون: | Sortino, Rosalba |
| المساهمون: | Gorostiza Langa, Pablo Ignacio, Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació |
| المصدر: | Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentació |
| بيانات النشر: | Universitat de Barcelona |
| سنة النشر: | 2023 |
| المجموعة: | Dipòsit Digital de la Universitat de Barcelona |
| مصطلحات موضوعية: | Fotofarmacologia, Fototeràpia, Radiació infraroja, Disseny de medicaments, Photopharmacology, Phototherapy, Infrared radiation, Drug design |
| الوصف: | [eng] G protein-coupled receptors (GPCRs) modulate diverse cellular responses to the majority of neurotransmitters and hormones within the human body. They exhibit much structural and functional diversity and are responsive to a plethora of ligands and stimuli including both endogenous (e.g., biogenic amines, cations, lipids, peptides, and glycoproteins) and exogenous (e.g., therapeutic drugs, photons, tastants, and odorants). Due to the key roles of GPCRs in a myriad of physiological processes, signaling pathways associated with GPCRs are implicated in the pathophysiology of various diseases, ranging from metabolic, immunological, and neurodegenerative disorders to cancer and infectious diseases. Approximately 40% of clinically approved drugs mediate their effects by modulating GPCR signaling pathways, which makes them attractive targets for drug screening and discovery. In this work, we focus on distinct GPCRs which are involved in vital pathways, such as the muscarinic acetylcholine receptors, subtype -1 and subtype -2 (M1 and M2 mAChRs; class A); the dopamine receptor 1 (D1R; class A), and the metabotropic glutamate 6 receptor (mGlu6 receptor; class C). Both M1 receptor (M1R) and M2 receptor (M2R) are important drug targets for several diseases that affect the central nervous system (CNS), including Alzheimer's disease, Parkinson’s disease (PD), schizophrenia, sleep disorders, and acute brain diseases. M2R also represent a target for cardiac disfunctions; the D1R for hypertension and PD, and mGlu6 receptor for retinal degenerative diseases, like retinitis pigmentosa. Traditional pharmacological approaches for the modulation of the GPCRs activity are still limited since precise spatiotemporal control of a ligand is lost as soon it is administrated. Photopharmacology proposes the use of small diffusible molecules called photochromic ligands (PCLs) (or photoswitches) to overcome this shortfall, since their activity can be reversibly controlled by light with high precision. In this thesis, we combined ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| وصف الملف: | 532 p.; application/pdf |
| اللغة: | English |
| العلاقة: | http://hdl.handle.net/2445/210883Test; http://hdl.handle.net/10803/690817Test |
| الإتاحة: | http://hdl.handle.net/2445/210883Test http://hdl.handle.net/10803/690817Test |
| حقوق: | (c) Sortino, Rosalba, 2024 ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.1A6405D3 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |