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Innovative peptides against cancer and pathogenic bacteria, with advances in science, biopharmaceutical drug development, product market targeting, training , and communication.

Deliverables

Outreaching Outputs

During the four years of INPACT we aim to achieve regular non-specialised press news by participating in the Researchers’ Nights, World Cancer Day, and the European Antibiotic Awareness Day. Technological achievements will be announced by joint international press releases; our goal is to have at least five different national news disseminated in the countries directly involved in the creation of those technologies during the course of INPACT. Open days will occur in each of the participating institutions and aim at having at least 60 visitors from general public, including students and patient association affiliates, five journalists, and two politicians with power to make decisions. We anticipate that members in INPACT team will be invited to participate into four, or more, public initiatives per year organized by third parties’.

Products

New technologies to be adopted by the partner SMEs or to be sold to third parties. The quantitative goal is to generate two drug leads to treat each of the following conditions: brain tumour, blood tumour and metastatic circulating cells, and MRSA infection. Inherent to the previous deliverable, new Intellectual Property Rights (IPR) will be built from existing IPR of the partners.

Dissemination Outputs

We expect to file at least three patents to protect new technologies. The patents are, by themselves, vehicles of dissemination but INPACT will also have R&D papers as deliverables. Our aim is to have at least six papers published in high-quality (Quartile 1 in impact factor ranking) international journals. We also aim at having three seminars and/or satellite meetings organized in the context of large-scale scientific meetings (>500 participants) and at presenting the results obtained within INPACT project in at least eight international conferences.

Training and career development

Training activities in INPACT will provide both intersectoral and international training, namely, i) Experience in working in non-academic environments (>4 months: training will be given by CEAMED, TCP, PTD or ICH to at least five PhD students) and ii) Experience in working with distinct cultural environment (>3 months in a foreign country to at least 10 ESRs). Additional information in Table 3 - Secondments description.

Publications

Psd1 Effects on Candida albicans Planktonic Cells and Biofilms

Author(s): Sónia Gonçalves, Patrícia M. Silva, Mário R. Felício, Luciano N. de Medeiros, Eleonora Kurtenbach, Nuno C. Santos
Published in: Frontiers in Cellular and Infection Microbiology, Issue 7, 2017, ISSN 2235-2988
DOI: 10.3389/fcimb.2017.00249

Peptides with Dual Antimicrobial and Anticancer Activities

Author(s): Mário R. Felício, Osmar N. Silva, Sônia Gonçalves, Nuno C. Santos, Octávio L. Franco
Published in: Frontiers in Chemistry, Issue 5, 2017, ISSN 1664-302X
DOI: 10.3389/fchem.2017.00005

New Potent Membrane-Targeting Antibacterial Peptides from Viral Capsid Proteins

Author(s): Susana A. Dias, João M. Freire, Clara Pérez-Peinado, Marco M. Domingues, Diana Gaspar, Nuno Vale, Paula Gomes, David Andreu, Sónia T. Henriques, Miguel A. R. B. Castanho, Ana S. Veiga
Published in: Frontiers in Microbiology, Issue 8, 2017, ISSN 1664-302X
DOI: 10.3389/fmicb.2017.00775

Pharmacological Potential of the Endogenous Dipeptide Kyotorphin and Selected Derivatives

Author(s): Juliana Perazzo, Miguel A. R. B. Castanho, Sónia Sá Santos
Published in: Frontiers in Pharmacology, Issue 7, 2017, ISSN 1663-9812
DOI: 10.3389/fphar.2016.00530

Neuropeptide Kyotorphin Impacts on Lipopolysaccharide-Induced Glucocorticoid-Mediated Inflammatory Response. A Molecular Link to Nociception, Neuroprotection, and Anti-Inflammatory Action

Author(s): Juliana Perazzo, Carla Lima, Montserrat Heras, Eduard Bardají, Mônica Lopes-Ferreira, Miguel Castanho
Published in: ACS Chemical Neuroscience, Issue 8/8, 2017, Page(s) 1663-1667, ISSN 1948-7193
DOI: 10.1021/acschemneuro.7b00007

A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model

Author(s): Sara Neves-Coelho, Rute Eleutério, Francisco Enguita, Vera Neves, Miguel Castanho
Published in: Molecules, Issue 22/10, 2017, Page(s) 1753, ISSN 1420-3049
DOI: 10.3390/molecules22101753

Endothelium-Mediated Action of Analogues of the Endogenous Neuropeptide Kyotorphin (Tyrosil-Arginine): Mechanistic Insights from Permeation and Effects on Microcirculation

Author(s): Juliana Perazzo, Mônica Lopes-Ferreira, Sónia Sá Santos, Isa Serrano, Antónia Pinto, Carla Lima, Eduard Bardaji, Isaura Tavares, Montserrat Heras, Katia Conceição, Miguel A. R. B. Castanho
Published in: ACS Chemical Neuroscience, Issue 7/8, 2016, Page(s) 1130-1140, ISSN 1948-7193
DOI: 10.1021/acschemneuro.6b00099

Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-Protoporphyrin IX, and Mesoporphyrin IX

Author(s): Christine Cruz-Oliveira, Andreza F. Almeida, João M. Freire, Marjolly B. Caruso, Maria A. Morando, Vivian N. S. Ferreira, Iranaia Assunção-Miranda, Andre M. O. Gomes, Miguel A. R. B. Castanho, Andrea T. Da Poian
Published in: Antimicrobial Agents and Chemotherapy, Issue 61/6, 2017, Page(s) e00053-17, ISSN 0066-4804
DOI: 10.1128/AAC.00053-17

Challenging metastatic breast cancer with the natural defensin PvD 1

Author(s): Tiago N. Figueira, Filipa D. Oliveira, Inês Almeida, Érica O. Mello, Valdirene M. Gomes, Miguel A. R. B. Castanho, Diana Gaspar
Published in: Nanoscale, Issue 9/43, 2017, Page(s) 16887-16899, ISSN 2040-3364
DOI: 10.1039/c7nr05872a

A polyalanine peptide derived from polar fish with anti-infectious activities

Author(s): Marlon H. Cardoso, Suzana M. Ribeiro, Diego O. Nolasco, César de la Fuente-Núñez, Mário R. Felício, Sónia Gonçalves, Carolina O. Matos, Luciano M. Liao, Nuno C. Santos, Robert E. W. Hancock, Octávio L. Franco, Ludovico Migliolo
Published in: Scientific Reports, Issue 6, 2016, Page(s) 21385, ISSN 2045-2322
DOI: 10.1038/srep21385

Antibody Approaches To Treat Brain Diseases

Author(s): Vera Neves, Frederico Aires-da-Silva, Sofia Corte-Real, Miguel A.R.B. Castanho
Published in: Trends in Biotechnology, Issue 34/1, 2016, Page(s) 36-48, ISSN 0167-7799
DOI: 10.1016/j.tibtech.2015.10.005

Shifting gear in antimicrobial and anticancer peptides biophysical studies: from vesicles to cells

Author(s): João M. Freire, Diana Gaspar, Ana Salomé Veiga, Miguel A. R. B. Castanho
Published in: Journal of Peptide Science, Issue 21/3, 2015, Page(s) 178-185, ISSN 1075-2617
DOI: 10.1002/psc.2741

Structural and functional evaluation of the palindromic alanine-rich antimicrobial peptide Pa-MAP2

Author(s): Ludovico Migliolo, Mário R. Felício, Marlon H. Cardoso, Osmar N. Silva, Mary-Ann E. Xavier, Diego O. Nolasco, Adeliana Silva de Oliveira, Ignasi Roca-Subira, Jordi Vila Estape, Leandro D. Teixeira, Sonia M. Freitas, Anselmo J. Otero-Gonzalez, Sónia Gonçalves, Nuno C. Santos, Octavio L. Franco
Published in: Biochimica et Biophysica Acta (BBA) - Biomembranes, Issue 1858/7, 2016, Page(s) 1488-1498, ISSN 0005-2736
DOI: 10.1016/j.bbamem.2016.04.003

Rethinking the capsid proteins of enveloped viruses: multifunctionality from genome packaging to genome transfection

Author(s): João M. Freire, Nuno C. Santos, Ana Salomé Veiga, Andrea T. Da Poian, Miguel A. R. B. Castanho
Published in: FEBS Journal, Issue 282/12, 2015, Page(s) 2267-2278, ISSN 1742-464X
DOI: 10.1111/febs.13274

New frontiers for anti-biofilm drug development

Author(s): Suzana M. Ribeiro, Mário R. Felício, Esther Vilas Boas, Sónia Gonçalves, Fabrício F. Costa, Ramar Perumal Samy, Nuno C. Santos, Octávio L. Franco
Published in: Pharmacology & Therapeutics, Issue 160, 2016, Page(s) 133-144, ISSN 0163-7258
DOI: 10.1016/j.pharmthera.2016.02.006

Peptibodies: An elegant solution for a long-standing problem

Author(s): Marco Cavaco, Miguel A. R. B. Castanho, Vera Neves
Published in: Peptide Science, Issue 110/1, 2018, Page(s) e23095, ISSN 2475-8817
DOI: 10.1002/bip.23095

Mechanisms of bacterial membrane permeabilization by crotalicidin (Ctn) and its fragment Ctn(15–34), antimicrobial peptides from rattlesnake venom

Author(s): Clara Pérez-Peinado, Susana Almeida Dias, Marco M. Domingues, Aurélie H. Benfield, João Miguel Freire, Gandhi Rádis-Baptista, Diana Gaspar, Miguel A. R. B. Castanho, David J. Craik, Sónia Troeira Henriques, Ana Salomé Veiga, David Andreu
Published in: Journal of Biological Chemistry, Issue 293/5, 2018, Page(s) 1536-1549, ISSN 0021-9258
DOI: 10.1074/jbc.ra117.000125

Fast and potent bactericidal membrane lytic activity of PaDBS1R1, a novel cationic antimicrobial peptide

Author(s): Luz N. Irazazabal, William F. Porto, Isabel C.M. Fensterseifer, Eliane S.F. Alves, Carolina O. Matos, Antônio C.S. Menezes, Mário R. Felício, Sónia Gonçalves, Nuno C. Santos, Suzana M. Ribeiro, Vincent Humblot, Luciano M. Lião, Ali Ladram, Octavio L. Franco
Published in: Biochimica et Biophysica Acta (BBA) - Biomembranes, Issue 1861/1, 2019, Page(s) 178-190, ISSN 0005-2736
DOI: 10.1016/j.bbamem.2018.08.001

Designing improved active peptides for therapeutic approaches against infectious diseases

Author(s): Bárbara Gomes, Marcelo T. Augusto, Mário R. Felício, Axel Hollmann, Octávio L. Franco, Sónia Gonçalves, Nuno C. Santos
Published in: Biotechnology Advances, Issue 36/2, 2018, Page(s) 415-429, ISSN 0734-9750
DOI: 10.1016/j.biotechadv.2018.01.004

Novel Peptides Derived from Dengue Virus Capsid Protein Translocate Reversibly the Blood–Brain Barrier through a Receptor-Free Mechanism

Author(s): Vera Neves , Frederico Aires-da-Silva, Maurício Morais, Lurdes Gano, Elisabete Ribeiro, Antónia Pinto, Sandra Aguiar, Diana Gaspar, Célia Fernandes, João D. G. Correia, and Miguel A. R. B. Castanho
Published in: ACS Chemical Biology, 2017, ISSN 1554-8929
DOI: 10.1021/acschembio.7b00087