Search results for: Conor R. Caffrey

Items from 1 to 20 out of 52 results

article

Antiparasitic Properties of Propolis Extracts and Their Compounds

Lucas A. L. Paula, Ana C. B. B. Cândido, Mario F. C. Santos, Conor R. Caffrey, more

Chemistry & Biodiversity > 18 > 9 > n/a - n/a

Propolis is a bee product that has been used in medicine since ancient times. Although its anti‐inflammatory, antioxidant, antimicrobial, antitumor, and immunomodulatory activities have been investigated, its anti‐parasitic properties remain poorly explored, especially regarding helminths. This review surveys the results obtained with propolis around the world against human parasites. Regarding protozoa,...

article

Uncovering Biological Application of Brazilian Green Propolis: A Phenotypic Screening against Schistosoma mansoni

Lucas A. de L. Paula, Mario F. C. Santos, Mariana C. Pagotti, Renata Faleiros, more

Chemistry & Biodiversity > 17 > 9 > n/a - n/a

The chemotherapy of schistosomiasis remains centered in the use of praziquantel, however, there has been growing resistant parasites to this drug. Thus, the aim of this work was to evaluate in vitro schistosomicidal activity of the hexanes/dichloromethane 1 : 1 extract of Brazilian green propolis (Pex), as well as its major isolated compounds artepillin C, caffeic acid, coumaric acid and drupanin...

article

Multi-center screening of the Pathogen Box collection for schistosomiasis drug discovery

Martina Maccesi, Pedro H. N. Aguiar, Valérian Pasche, Melody Padilla, more

Parasites & Vectors > 2019 > 12 > 1 > 1-10

Background Over the past five years, as a public service to encourage and accelerate drug discovery for diseases of poverty, the Medicines for Malaria Venture (MMV) has released box sets of 400 compounds named the Malaria, Pathogen and Stasis Boxes. Here, we screened the Pathogen Box against the post-infective larvae (schistosomula) of Schistosoma mansoni using assays particular to the three contributing...

article

Molecular characterization and functional analysis of the Schistosoma mekongi Ca²⁺-dependent cysteine protease (calpain)

Salisa Chaimon, Yanin Limpanont, Onrapak Reamtong, Sumate Ampawong, more

Parasites & Vectors > 2019 > 12 > 1 > 1-18

Background Schistosoma mekongi, which causes schistosomiasis in humans, is an important public health issue in Southeast Asia. Treatment with praziquantel is the primary method of control but emergence of praziquantel resistance requires the development of alternative drugs and vaccines. Calcium-dependent cysteine protease (calpain) is a novel vaccine candidate that has been studied in S. mansoni,...

article

High Throughput and Computational Repurposing for Neglected Diseases

Helen W. Hernandez, Melinda Soeung, Kimberley M. Zorn, Norah Ashoura, more

Pharmaceutical Research > 2019 > 36 > 2 > 1-20

Purpose Neglected tropical diseases (NTDs) represent are a heterogeneous group of communicable diseases that are found within the poorest populations of the world. There are 23 NTDs that have been prioritized by the World Health Organization, which are endemic in 149 countries and affect more than 1.4 billion people, costing these developing economies billions of dollars annually. The NTDs result...

article

Targeting proteasomes in infectious organisms to combat disease

Betsaida Bibo‐Verdugo, Zhenze Jiang, Conor R. Caffrey, Anthony J. O'Donoghue

The FEBS Journal > 284 > 10 > 1503 - 1517

Proteasomes are multisubunit, energy‐dependent, proteolytic complexes that play an essential role in intracellular protein turnover. They are present in eukaryotes, archaea, and in some actinobacteria species. Inhibition of proteasome activity has emerged as a powerful strategy for anticancer therapy and three drugs have been approved for treatment of multiple myeloma. These compounds react covalently...

article

Anthelmintics: From discovery to resistance II (San Diego, 2016)

Richard J. Martin, Adrian J. Wolstenholme, Conor R. Caffrey

International Journal for Parasitology: Drugs and Drug Resistance > 2016 > 6 > 3 > 297-298

The second scientific meeting in the series: “Anthelmintics: From Discovery to Resistance” was held in San Diego in February, 2016. The focus topics of the meeting, related to anthelmintic discovery and resistance, were novel technologies, bioinformatics, commercial interests, anthelmintic modes of action and anthelmintic resistance. Basic scientific, human and veterinary interests were addressed...

article

Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles

Jan Dvořák, Pavla Fajtová, Lenka Ulrychová, Adrian Leontovyč, more

Biochimie > 2016 > 122 > C > 99-109

Schistosomiasis is one of a number of chronic helminth diseases of poverty that severely impact personal and societal well-being and productivity. Peptidases (proteases) are vital to successful parasitism, and can modulate host physiology and immunology. Interference of peptidase action by specific drugs or vaccines can be therapeutically beneficial. To date, research on peptidases in the schistosome...

chapter

Cysteine Peptidases of Kinetoplastid Parasites

Conor R. Caffrey, Ana-Paula Lima, Dietmar Steverding

Advances in Experimental Medicine and Biology > Cysteine Proteases of Pathogenic Organisms > 84-99

We review Clan CA Family C1 peptidases of kinetoplastid parasites (Trypanosoma and Leishmania) with respect to biochemical and genetic diversity, genomic organization and stage-specificity and control of expression. We discuss their contributions to parasite metabolism, virulence and pathogenesis and modulation of the host’s immune response. Their applications as vaccine candidates and diagnostic...

article

Activation Route of the Schistosoma mansoni Cathepsin B1 Drug Target: Structural Map with a Glycosaminoglycan Switch

Adéla Jílková, Martin Horn, Pavlína Řezáčová, Lucie Marešová, more

Structure > 2014 > 22 > 12 > 1786-1798

Cathepsin B1 (SmCB1) is a digestive protease of the parasitic blood fluke Schistosoma mansoni and a drug target for the treatment of schistosomiasis, a disease that afflicts over 200 million people. SmCB1 is synthesized as an inactive zymogen in which the N-terminal propeptide blocks the active site. We investigated the activation of the zymogen by which the propeptide is proteolytically removed and...

article

Serum albumin and α-1 acid glycoprotein impede the killing of Schistosoma mansoni by the tyrosine kinase inhibitor Imatinib

Svenja Beckmann, Thavy Long, Christina Scheld, Rudolf Geyer, more

International Journal for Parasitology: Drugs and Drug Resistance > 2014 > 4 > 3 > 287-295

In the search for new drugs and drug targets to treat the flatworm disease schistosomiasis, protein kinases (PKs) have come under particular scrutiny because of their essential roles in developmental and physiological processes in schistosome parasites. In this context the application of the anti-cancer Abl tyrosine kinase (TK) inhibitor Imatinib (Gleevec/Glivec; STI-571) to adult Schistosoma mansoni...

article

New insights into the machinery of blood digestion by ticks

Daniel Sojka, Zdeněk Franta, Martin Horn, Conor R. Caffrey, more

Trends in Parasitology > 2013 > 29 > 6 > 276-285

Blood-protein digestion is a key physiological process providing essential nutrients for ticks and is a prerequisite for the transmission of tick-borne pathogens. Recently, substantial progress has been made in determining the proteolytic machinery in tick gut tissue, which is based on a dynamic multienzyme network capable of processing a vast amount of host blood. In this article we summarize our...

article

Trypanosoma brucei: Chemical evidence that cathepsin L is essential for survival and a relevant drug target

Dietmar Steverding, Darren W. Sexton, Xia Wang, Sebastian S. Gehrke, more

International Journal for Parasitology > 2012 > 42 > 5 > 481-488

The protozoan parasite causing human African trypanosomiasis, Trypanosoma brucei, displays cysteine peptidase activity, the chemical inhibition of which is lethal to the parasite. This activity comprises a cathepsin B (TbCATB) and a cathepsin L (TbCATL). Previous RNA interference (RNAi) data suggest that TbCATB rather than TbCATL is essential to survival even though silencing of the latter was incomplete...

article

Schistosoma comparative genomics: integrating genome structure, parasite biology and anthelmintic discovery

Martin T. Swain, Denis M. Larkin, Conor R. Caffrey, Stephen J. Davies, more

Trends in Parasitology > 2011 > 27 > 12 > 555-564

Schistosoma genomes provide a comprehensive resource for identifying the molecular processes that shape parasite evolution and for discovering novel chemotherapeutic or immunoprophylactic targets. Here, we demonstrate how intragenus and intergenus comparative genomics can be used to drive these investigations forward, illustrate the advantages and limitations of these approaches and review how post-genomic...

article

IrCL1 – The haemoglobinolytic cathepsin L of the hard tick, Ixodes ricinus

Zdenek Franta, Daniel Sojka, Helena Frantova, Jan Dvorak, more

International Journal for Parasitology > 2011 > 41 > 12 > 1253-1262

Intracellular proteolysis of ingested blood proteins is a crucial physiological process in ticks. In our model tick, Ixodes ricinus, cathepsin L (IrCL1) is part of a gut-associated multi-peptidase complex; its endopeptidase activity is important in the initial phase of haemoglobinolysis. We present the functional and biochemical characterisation of this enzyme. We show, by RNA interference (RNAi),...

article

From innovation to application: Social–ecological context, diagnostics, drugs and integrated control of schistosomiasis

Jürg Utzinger, Eliézer K. N’Goran, Conor R. Caffrey, Jennifer Keiser

Acta Tropica > 2011 > 120 > Supplement 1 > S121-S137

Compared to malaria, tuberculosis and HIV/AIDS, schistosomiasis remains a truly neglected tropical disease. Schistosomiasis, perhaps more than any other disease, is entrenched in prevailing social–ecological systems, since transmission is governed by human behaviour (e.g. open defecation and patterns of unprotected surface water contacts) and ecological features (e.g. living in close proximity to...

article

Mapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors

Martin Horn, Adéla Jílková, Jiří Vondrášek, Lucie Marešová, more

ACS Chemical Biology > 2011 > 6 > 6 > 609 - 617

article

Biolistic transformation of Schistosoma mansoni: Studies with modified reporter-gene constructs containing regulatory regions of protease genes

Jan Dvořák, Svenja Beckmann, Kee-Chong Lim, Juan C. Engel, more

Molecular & Biochemical Parasitology > 2010 > 170 > 1 > 37-40

Biolistics of the flatworm parasite Schistosoma mansoni facilitates the accurate spatial expression of transgenes under the control of gene-specific promoter elements. To improve transgene expression, either in the number of positive worms and/or an increased transgene signal per worm, we tested plasmid constructs incorporating 5′ and 3′ gene-specific genomic fragments, and parts of the open reading...

article

Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases)

Asli Ovat, Fanuel Muindi, Crystal Fagan, Michelle Brouner, more

Journal of Medicinal Chemistry > 2009 > 52 > 22 > 7192 - 7210

article

Hemoglobin Digestion in Blood-Feeding Ticks: Mapping a Multipeptidase Pathway by Functional Proteomics

Martin Horn, Martina Nussbaumerová, Miloslav Šanda, Zuzana Kovářová, more

Chemistry & Biology > 2009 > 16 > 10 > 1053-1063

Hemoglobin digestion is an essential process for blood-feeding parasites. Using chemical tools, we deconvoluted the intracellular hemoglobinolytic cascade in the tick Ixodes ricinus, a vector of Lyme disease and tick-borne encephalitis. In tick gut tissue, a network of peptidases was demonstrated through imaging with specific activity-based probes and activity profiling with peptidic substrates and...

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INFONA - science communication portal

Search results for: Conor R. Caffrey

Antiparasitic Properties of Propolis Extracts and Their Compounds

Uncovering Biological Application of Brazilian Green Propolis: A Phenotypic Screening against Schistosoma mansoni

Multi-center screening of the Pathogen Box collection for schistosomiasis drug discovery

Molecular characterization and functional analysis of the Schistosoma mekongi Ca²⁺-dependent cysteine protease (calpain)

High Throughput and Computational Repurposing for Neglected Diseases

Targeting proteasomes in infectious organisms to combat disease

Anthelmintics: From discovery to resistance II (San Diego, 2016)

Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles

Cysteine Peptidases of Kinetoplastid Parasites

Activation Route of the Schistosoma mansoni Cathepsin B1 Drug Target: Structural Map with a Glycosaminoglycan Switch

Serum albumin and α-1 acid glycoprotein impede the killing of Schistosoma mansoni by the tyrosine kinase inhibitor Imatinib

New insights into the machinery of blood digestion by ticks

Trypanosoma brucei: Chemical evidence that cathepsin L is essential for survival and a relevant drug target

Schistosoma comparative genomics: integrating genome structure, parasite biology and anthelmintic discovery

IrCL1 – The haemoglobinolytic cathepsin L of the hard tick, Ixodes ricinus

From innovation to application: Social–ecological context, diagnostics, drugs and integrated control of schistosomiasis

Mapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors

Biolistic transformation of Schistosoma mansoni: Studies with modified reporter-gene constructs containing regulatory regions of protease genes

Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases)

Hemoglobin Digestion in Blood-Feeding Ticks: Mapping a Multipeptidase Pathway by Functional Proteomics

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