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Castanho, Miguel
Lab

Physical Biochemistry of Drugs & Targets

Our goal is to unravel the physical principles that govern interactions at the molecular level of several clinically relevant compounds with model cell systems, with the objectives of developing new drugs and better understand the mechanism of action of already established ones.

PEP2BRAIN Project

Advanced Training

Science and Society

  • Research Areas

    • Analgesic peptides
    • Antimicrobial peptides
    • Cell-penetrating peptides
    • Viral fusion inhibitors
    • Anticancer Peptides
  • Research Team

    • Ongoing Research Projects

      • 2018/2021 - Fighting Zika virus with antiviral peptides and conjugates translocating blood-placental and blood-brain barriers. Coordinator: David Andreu Martinez, Universitat Pompeu Fabra. Coordinator at iMM: Miguel Castanho. Funding Agency: Fundación Bancaria "la Caixa". Reference: HR17-00409.

      • 2018/2021 - Selecção de fármacos líder anti-virus zika capazes de translocar as barreiras hemato-placentária e hemato-encefálica. Combinando péptidos translocadores inovadores e eficazes com novos antivirais para alcançar o vírus Zika através de barreiras. Coordinator: Carla Couto. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: PTDC/BIA-VIR/29495/2017.

      • 2018/2021 - Validação polifásica de péptidos antimicrobianos como tratamento alternativo para infecções do pé diabético. Coordinator: Manuela Oliveira, Faculdade de Medicina Veterinária da ULisboa. Coordinator at iMM: Ana Salomé Veiga. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: PTDC/SAU-INF/28466/2017.

      • 2018/2021 - Combinando métodos computacionais e experimentais para obter uma caracterização genérica dos péptidos de fusão de vírus. Coordinator: Diana Lousa, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa. Coordinator at iMM: Ana Salomé Veiga. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: PTDC/CCI-BIO/28200/2017.

      • 2018/2021 - ADC1.1: Desenvolvimento de uma nova classe de moléculas de conjugados de anticorpos para o tratamento do cancro. Coordinator: Frederico Aires-Silva, Faculdade de Medicina Veterinária da ULisboa. Coordinator at iMM: Vera Neves. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: ADC1.1 - LISBOA-01-0145-FEDER-032085.

      • 2018/2021 - Dadores de gasotransmissores NO e H2S terapêuticos baseados em materiais nanoporosos. Coordinator: Moisés Pinto, Instituto Superior Técnico da ULisboa. Coordinator at iMM: Ana Herdade. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: PTDC/MED-QUI/28721/2017.

      • 2016/2019 - Towards the development of innovative highly effective dual action anti-HIV peptides. Coordinator: Ana Salomé Veiga. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: PTDC/QEQ-MED/4412/2014.

      • 2016/2019 - Cell-cell communication in metastatic breast cancer: a control point that can lead to breast cancer treatment. Coordinator: Diana Gaspar. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: PTDC/BBB-BQB/1693/2014.

      • 2016/2019 - Overcoming the Brain Drug Delivery Bottleneck: Development of single domain antibodies for brain targeting and drug delivery across the Blood-Brain Barrier. Coordinator: Frederico Aires-Silva, Faculdade de Medicina Veterinária da ULisboa. Coordinator at iMM: Vera Neves. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: PTDC/BBB-BIO/0508/2014.

      • 2016/2019 - Alzheimer3D: Trifunctional Conjugates for the Selective Drug Delivery in Alzheimer’s Disease. Coordinator: Rudi Oliveira, Faculdade de Farmácia da ULisboa. Coordinator at iMM: Vera Neves. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: PTDC/QEQ-MED/5512/2014.

      • 2016/2019 - Peptides for blood-brain barrier transmigration and drug delivery - novel therapies for the central nervous system. Coordinator: Vera Neves. Funding Agency: Fundação para a Ciência e a Tecnologia. Reference: PTDC/BBB-NAN/1578/2014.

      • 2015/2019 - INPACT: Innovative peptides against cancer and pathogenic bacteria, with advances in science, biopharmaceutical drug development, product market targeting, training, and communication. Coordinator: Miguel Castanho. Funding Agency: European Commission. Reference: MSCA RISE 644167.

    • Prizes

      • 2019  - Miguel Castanho – Scientific Award University of Lisbon / Caixa Geral de Depósitos 2018 in the scientific area of ​​Biomedical Sciences.

      • 2019 – Tiago N. Figueira – SPBf Young Biophysicist 2019 Prize - Structure−Stability−Function Mechanistic Links in the Anti-Measles Virus Action of Tocopherol-Derivatized Peptide Nanoparticles" ACS Nano 12, 9855-9865

      • 2018 - Filipa D. Oliveira - Prize for best poster at the Lisbon Biophysics Networking Meeting: From Protein Dynamics to Membrane Biophysics (Awarded on Oct 12)

      • 2017 – Tiago N. Figueira - PROLAB Award 2017. “Pathogenesis of measles virus and antiviral approaches to treatment”, Supervised by Matteo Porotto and Anne Moscona, Columbia University Medical Center, NY, NY, USA

      • 2015  - Grünenthal Foundation, DOR Award, Clinical Research – By the study of drugs for Alzheimer's disease and chronic pain

      • 2014  - Miguel Castanho - Leonidas Zervas award of the European Peptide Society for achievements in Peptide Science

      • 2012/2015 - Miguel Castanho - Special visiting researcher em Medical Biochemistry (Post graduation and Outreach Programs) Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Brasil

      • 2012 - Miguel Castanho - Named International Local Embassador by the Biochemical Society UK

      • 2011 - Miguel Castanho - Featured in the section “Biophysicist in profile” (Biophysical Society USA Newsletter), June 2011. 

      • 2010 - Marta Ribeiro, Henri Franquelim -I2P-Ideas to products, 2nd ranked team in European Entrepreneurship competition (Aachen, Germany) com “a peptide-based technology to translocate the Blood-brain Barrier.”

      • 2009 - Grünenthal Foundation, DOR Award (2008), Basic Science – By the study of the analgesic neuropeptide analgesic kyotorphin

      • 2005 - Miguel Castanho - Award Prof José Luis Champalimaud, Secretariado Nacional para a Saúde, Ministério da Saúde, by contributing to the study of innovative drugs against HIV 

      • 2004 - Miguel Castanho - Award Dr. José Luis Champalimaud, Comissão Nacional de Luta Contra a Sida, by the contribution to the study of the mechanism of action of anti-HIV peptide drugs 

      • 2004 - Miguel Castanho - Medal Vicente de Seabra, Sociedade Portuguesa de Química, by the contribution to the Development of Chemistry and early career 

    • Selected Publications

      • 2018

      - Figueira TN, Mendonça DA, Gaspar D, Melo MN, Moscona A, Porotto M, Castanho MARB, Veiga AS. (2018) Structure-Stability-Function Mechanistic Links in the Anti-Measles Virus Action of Tocopherol-Derivatized Peptide Nanoparticles. ACS Nano. DOI: 10.1021/acsnano.8b01422, 12 (10), 9855-9865.

      - Figueira TN, Augusto MT, Rybkina K, Stelitano D, Noval MG, Harder OE, Veiga AS, Huey D, Alabi CA, Biswas S, Niewiesk S, Moscona A, Santos NC, Castanho MARB, Porotto M. (2018) Effective in Vivo Targeting of Influenza Virus through a Cell-Penetrating/Fusion Inhibitor Tandem Peptide Anchored to the Plasma Membrane. Bioconjug Chem. DOI: 10.1021/acs.bioconjchem.8b00527, 29 (10), 3362-3376.

       

       

       

       

      - Pérez-Peinado C, Dias SA, Domingues MM, Benfield AH, Freire JM, Radis-Baptista G, Gaspar D, Castanho MARB, Craik DJ, Henriques ST, Veiga AS, Andreu D (2018) Mechanism of bacterial membrane permeabilization of crotalicidin (Ctn) and its fragment Ctn[15-34], antimicrobial peptides from rattlesnake venom. J Biol Chem. DOI: 10.1074/jbc.RA117.000125, 293 (5), 1536–1549.  

       

      • 2017

      - Neves V, Aires da Silva F, Morais M, Gano L, Ribeiro E, Pinto A, Aguiar S, Gaspar D, Fernandes C, Correia JDG, Castanho MARB. (2017) Novel peptides derived from Dengue virus capsid protein translocate reversibly the blood-brain barrier through a receptor-free mechanism. ACS Chem Biol. DOI: 10.1021/acschembio.7b00087, 12 (5), 1257-1268.

      - Dias SA, Freire JM, Pérez-Peinado C, Domingues MM, Gaspar D, Vale N, Gomes P, Andreu D, Henriques ST, Castanho M, Veiga AS. (2017) New Potent Membrane-Targeting Antibacterial Peptides from Viral Capsid Proteins. Front Microbiol. DOI: 10.3389/fmicb.2017.00775, 8, 775.

      - FigueiraTN, FreireJM, Cunha-SantosC, HerasM, GonçalvesJ, Moscona A, PorottoM, VeigaAS, CastanhoMARB. (2017) Quantitative analysis of molecular partition towards lipid membranes using surface plasmon resonance. Sci. Rep. DOI: 10.1038/srep45647, 7, 45647.

      - Freire JM, de Figueiredo IR, Valle J, Veiga AS, Andreu D, Enguita FJ, Castanho MARB. (2017) siRNAcell-penetrating peptides complexes as a combinatorial therapy against chronic myeloid leukemia using BV173 cell line as model. J Control Release. DOI: 10.1016/j.jconrel.2016.11.027, 245, 127-136.

      - Figueira TN, Oliveira FD, Almeida I, Mello ÉO, Gomes VM, Castanho MARB, Gaspar D. (2017) Challenging metastatic breast cancer with the natural defensin PvD1, Nanoscale. DOI: 10.1039/c7nr05872a, 9(43): 16887-16899.

      - Figueira TN*, Palermo LM*, Veiga AS*, Huey D, Alabi CA, Santos NC, Welsch JC, Mathieu C, Horvat B, Niewiesk S, Moscona A, Castanho MARB, Porotto M. (2017) In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence. J. Virol. 91. DOI: 10.1128/JVI.01554-16, e01554-16. (*Authors with equal contribution)

      - Perazzo J, Lima C, Heras M, Bardají E, Lopes-Ferreira M, Castanho, MARB. (2017) Neuropeptide kyotorphin impacts on lipopolysaccharide-induced glucocorticoid-mediated inflammatory response. A molecular link to nociception, neuroprotection, and anti-inflammatory action. ACS chemical neuroscience, 8, 1663-1667.

       

      • 2016

      - Perazzo J, Lopes-Ferreira M, Sá Santos S, Serrano I, Pinto A, Lima C, Bardaji E, Tavares I, Heras M, Conceição K. (2016) Endothelium-mediated action of analogues of the endogenous neuropeptide kyotorphin (tyrosil-arginine): mechanistic insights from permeation and effects on microcirculation ACS chemical neuroscience, 7, 1130-1140.

      - Neves V, Aires da Silva F, Corte-Real S, Castanho MARB. (2016) Antibody approaches to treat brain illnesses. Trends in biotechnology. DOI:10.1016/j.tibtech.2015.10.005, 24 (1), 36-48.

       

      • 2015

      - Freire JM, Dias SA, Flores L, Veiga AS, Castanho M. (2015) Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides. Bioinformatics. DOI: 10.1093/bioinformatics/btv131, 31, 2252-2256.

      - Freire JM, Gaspar D, Veiga AS, Castanho MA. (2015) Shifting gear in antimicrobial and anticancer peptides biophysical studies: from vesicles to cells. J Pept Sci. DOI: 10.1002/psc.2741, 21, 178-185. 

      - Freire JM, Gaspar D, de la Torre BG, Veiga AS, Andreu D, Castanho MARB. (2015)Monitoring antibacterial permeabilization in real time using time-resolved flow cytometry. Biochim Biophys Acta – Biomembranes. DOI: 10.1016/j.bbamem.2014.11.001, 1848, 554-560. 

       

      • 2014

      - Freire JM, Veiga AS, de Figueiredo IR, de la Torre BG, Santos NC, Andreu D, Da Poian AT, Castanho MARB. (2014)Nucleic acid delivery by cell penetrating peptides derived from Dengue virus capsid protein. Design and mechanism of action. FEBS J. DOI: 10.1111/febs.12587, 281, 191-215. 

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