6 documents found, page 1 of 1
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascu...
Mahú, Inês; Barateiro, Andreia; Rial-Pensado, Eva; Martinéz-Sánchez, Noelia; Vaz, Sandra H.; Cal, Pedro M.S.D.; Jenkins, Benjamin; Rodrigues, Tiago M.Anti-obesity drugs in the amphetamine (AMPH) class act in the brain to reduce appetite and increase locomotion. They are also characterized by adverse cardiovascular effects with origin that, despite absence of any in vivo evidence, is attributed to a direct sympathomimetic action in the heart. Here, we show that the cardiac side effects of AMPH originate from the brain and can be circumvented by PEGylation (PE...
Evaluation of linker length effects on a BET bromodomain probe
Traquete, Rui; Henderson, Elizabeth; Picaud, Sarah; Cal, Pedro M.S.D.; Sieglitz, Florian; Rodrigues, Tiago; Oliveira, Rudi; Filippakopoulos, PanagisFueled by the therapeutic potential of the epigenetic machinery, BET bromodomains have seen high interest as drug targets. Herein, we introduce different linkers to a BET bromodomain benzodiazepine ligand (I-BET762) to gauge its implications in the development of hybrid drugs, imaging probes and small molecule drug conjugates. Biophysical studies confirmed minimal disruption to binding of the BRD4 cavity by the...
Site-selective installation of BASHY fluorescent dyes to Annexin V for targeted...
Cal, Pedro M.S.D.; Sieglitz, Florian; Santos, Fábio; Parente Carvalho, Cátia; Guerreiro, Ana; Bertoldo, Jean B.; Pischel, Uwe; Gois, Pedro M. P.Fluorophores are indispensable for imaging biological processes. We report the design and synthesis of azide-tagged boronic acid salicylidenehydrazone (BASHY) dyes and their use for site-selective labelling of Annexin V. The Annexin V-BASHY conjugate maintained function and fluorescence as demonstrated by the targeted detection of apoptotic cells.
Nickel-Catalyzed Azide–Alkyne Cycloaddition to access 1,5-Disubstituted 1,2,3-T...
Kim, Woo Gyum; Kang, Mi Eun; Lee, Jae Bin; Jeon, Min Ho; Lee, Sungmin; Lee, Jungha; Choi, Bongseo; Cal, Pedro M.S.D.; Kang, Sebyung; Kee, Jung-MinTransition-metal-catalyzed or metal-free azide-alkyne cycloadditions are methods to access 1,4- or 1,5-disubstituted 1,2,3-triazoles. Although the copper-catalyzed cycloaddition to access 1,4-disubstituted products has been applied to biomolecular reaction systems, the azide-alkyne cycloaddition to access the complementary 1,5-regioisomers under aqueous and ambient conditions remains a challenge due to limited ...
Unveiling Englerin A as a modulator of L-type calcium channels
Rodrigues, Tiago; Sieglitz, Florian; Somovilla, Víctor J.; Cal, Pedro M.S.D.; Galione, Antony; Corzana, Francisco; Bernardes, Gonçalo J. L.The voltage-dependent L-type Ca(2+) channel was identified as a macromolecular target for (-)-englerin A. This finding was reached by using an unprecedented ligand-based prediction platform and the natural product piperlongumine as a pharmacophore probe. (-)-Englerin A features high substructure dissimilarity to known ligands for voltage-dependent Ca(2+) channels, selective binding affinity for the dihydropyrid...
Intramolecular C–H insertion catalyzed by dirhodium(II) complexes using CO2 as ...
Zakrzewska, Malgorzata E.; Cal, Pedro M.S.D.; Candeias, Nuno R.; Lukasik, Rafal M.; Afonso, Carlos A.M.; Ponte, Manuel Nunes; Gois, Pedro M.P.In this work, the intramolecular C–H insertion of diazoacetamides catalyzed by dirhodium(II) complexes and using CO2 as solvent is disclosed. The expected lactams were obtained in yields over 97%. The asymmetric intramolecular C–H insertion was also achieved and the β-lactam 14 was obtained in >97% yield and 65% ee using the chiral dirhodium(II) catalyst Rh2(S-PTTL)4. Finally, the dirhodium(II) complex Rh2(OAc)...