19 documents found, page 1 of 2
The World of GPCR dimers - Mapping dopamine receptor D2 homodimers in different...
Bueschbell, Beatriz; Magalhães, Pedro R.; Barreto, Carlos A. V.; Melo, Rita; Schiedel, Anke C.; Machuqueiro, Miguel; Moreira, Irina S.G protein-coupled receptors (GPCRs) are known to dimerize, but the molecular and structural basis of GPCR dimers is not well understood. In this study, we developed a computational framework to generate models of symmetric and asymmetric GPCR dimers using different monomer activation states and identified their most likely interfaces with molecular details. We chose the dopamine receptor D2 (D2R) homodimer as a...
Synthesis and the in vitro evaluation of antitumor activity of novel thiobenzan...
Álvaro Martins, Maria Joao; Railean, Violeta; Martins, Filomena; Machuqueiro, Miguel; Pacheco, Rita; Santos, SusanaCancer is a generic term for a large group of diseases that are the second-leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. Melanoma is a highly aggressive skin tumor with an increasing incidence and poor prognosis in the metastatic stage. Breast cancer still stands as one of the major cancer-associated deaths among women, and diagnosed cases are increasing year after year worl...
Multiplexed cellular profiling identifies an organoselenium compound as an inhi...
Jimenez, Lucia; Mayoral‐Varo, Victor; Amenábar, Carlos; Ortega, Judit; Sequeira, João G. N.; Machuqueiro, Miguel; Mourato, Cristiana; Silvestri, RomanoChromosomal region maintenance 1 (CRM1 also known as Xpo1 and exportin-1) is the receptor for the nuclear export controlling the intracellular localization and function of many cellular and viral proteins that play a crucial role in viral infections and cancer. The inhibition of CRM1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses, for the treatment of cancer, and...
Unveiling molecular details behind improved activity at neutral to alkaline pH ...
Borges, Patrícia T.; Silva, Diogo; Silva, Tomás F.D.; Brissos, Vânia; Cañellas, Marina; Lucas, Maria Fátima; Masgrau, Laura; Melo, EduardoDyP-type peroxidases (DyPs) are microbial enzymes that catalyze the oxidation of a wide range of substrates, including synthetic dyes, lignin-derived compounds, and metals, such as Mn2+ and Fe2+, and have enormous biotechnological potential in biorefineries. However, many questions on the molecular basis of enzyme function and stability remain unanswered. In this work, high-resolution structures of PpDyP wild-t...
Novel "ruthenium cyclopentadienyl" - peptide conjugate complexes against human ...
Machado, João Franco; Machuqueiro, Miguel; Marques, Fernanda; Robalo, M. Paula; Piedade, M. Fatima M.; Garcia, M. Helena; Correia, João D. G.In this work we explored the possibility of improving the selectivity of a cytotoxic Ru complex [RuCp(PPh3)(2,2'-bipy)][CF3SO3] (where Cp = eta(5)-cyclopentadienyl) TM34 towards FGFR(+) breast cancer cells. Molecular dynamics (MD) simulations of TM34 in a phosphatidylcholine membrane model pinpointed the cyclopentadienyl group as a favorable derivatization position for the peptide conjugation approach. Three ne...
Bioactivities of centaurium erythraea (Gentianaceae) decoctions: antioxidant ac...
Guedes, Laura; Reis, Pedro B. P. S.; Machuqueiro, Miguel; RESSAISSI, Asma; Pacheco, Rita; Serralheiro, Maria LuisaCentaurium erythraea is recommended for the treatment of gastrointestinal disorders and to reduce hypercholesterolemia in ethno-medicinal practice. To perform a top-down study that could give some insight into the molecular basis of these bioactivities, decoctions from C. erythraea leaves were prepared and the compounds were identified by liquid chromatography-high resolution tandemmassspectrometry(LC–MS/MS).Sec...
Proactive response to tackle the threat of emerging drugs: Synthesis and toxici...
Gaspar, Helena; Bronze, Soraia; Oliveira, Catarina; Victor, Bruno; Machuqueiro, Miguel; Pacheco, Rita; Caldeira, Maria João; Santos, SusanaThe emergence of potentially dangerous new psychoactive substances (NPS) imposes enormous challenges on forensic laboratories regarding their rapid and unambiguous identification. Access to comprehensive databases is essential for a quick characterization of these substances, allowing them to be categorized according to national and international legislations. In this work, it is reported the synthesis and stru...
Bioactivities of decoctions from Plectranthus species related to their traditio...
Brito, Elsa; Gomes, Emma; Fale, Pedro; Borges, Carlos; Pacheco, Rita; Teixeira, Vítor; Machuqueiro, Miguel; Ascensão, Lia; Serralheiro, Maria LuisaEthnopharmacological relevance Decoctions of Plectranthus species are traditionally ingested after large meals for treatment of food digestion and alcohol abuse. Aim of the study This study aims at associating the digestion-related ethno-uses of Plectranthus species decoctions to molecular mechanism that might explain them: easing digestion (AChE inhibition) and treating hangover (ADH inhibition) Material and m...
Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes
Dias, Catarina; Pais, João P.; Nunes, Rafael; Blázquez-Sánchez, Maria-Teresa; Marquês, Joaquim T.; Almeida, Andreia F.; Serra, Patrícia; Xavier, Nuno M.Anthrax is an infectious disease caused by Bacillus anthracis, a bioterrorism agent that develops resistance to clinically used antibiotics. Therefore, alternative mechanisms of action remain a challenge. Herein, we disclose deoxy glycosides responsible for specific carbohydrate-phospholipid interactions, causing phosphatidylethanolamine lamellar-to-inverted hexagonal phase transition and acting over B. anthrac...
Proactive response to tackle the threat of emerging drugs: synthesis and toxici...
Gaspar, Helena; Bronze, Soraia; Oliveira, Catarina; Victor, Bruno L.; Machuqueiro, Miguel; Pacheco, Rita; Caldeira, Maria João; Santos, SusanaThe emergence of potentially dangerous new psychoactive substances (NPS) imposes enormous challenges on forensic laboratories regarding their rapid and unambiguous identification. Access to comprehensive databases is essential for a quick characterization of these substances, allowing them to be categorized according to national and international legislations. In this work, it is reported the synthesis and stru...