Potassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus ()

International audiencePotassium (K(+)) channels are trans-membrane proteins, which play a key role in cellular excitability and signal transduction pathways. Scorpion toxins blocking the ion-conducting pore from the external side have been invaluable probes to elucidate the structural, functional, and physio-pathological characteristics of these ion channels. This review will focus on the interaction between K(+) channels and their peptide blockers isolated from the venom of the scorpion Tityus serrulatus, which is considered as the most dangerous scorpion in Brazil, in particular in Minas-Gerais State, where many casualties are described each year. The primary mechanisms of action of these K(+) blockers will be discussed in correlation with their structure, very often non-canonical compared to those of other well known K(+) channels blockers purified from other scorpion venoms. Also, special attention will be brought to the most recent data obtained by proteomic and transcriptomic analyses on Tityus serrulatus venoms and venom glands

New cassane diterpenes from caesalpinia echinata

Submitted by Nuzia Santos ([email protected]) on 2014-10-20T14:40:53Z No. of bitstreams: 1 New cassane diterpenes from Caesalpinia echinata.pdf: 322346 bytes, checksum: 005703ead6a099cb8967af34862ebd55 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2014-10-20T14:44:28Z (GMT) No. of bitstreams: 1 New cassane diterpenes from Caesalpinia echinata.pdf: 322346 bytes, checksum: 005703ead6a099cb8967af34862ebd55 (MD5)Made available in DSpace on 2014-10-20T14:44:28Z (GMT). No. of bitstreams: 1 New cassane diterpenes from Caesalpinia echinata.pdf: 322346 bytes, checksum: 005703ead6a099cb8967af34862ebd55 (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Química de Produtos Naturais. Belo Horizonte, MG, BrazilUniversidade Estadual do Sudoeste de Bahia. Jequié, BA, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Química de Produtos Naturais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Pesquisas Clínicas. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Química de Produtos Naturais. Belo Horizonte, MG, BrazilAn investigation of the ethanolic extract from stems of Caesalpinia echinata Lam Leguminosae-Caesalpinioideae) led to the isolation of five new cassane diterpenes along with known lambertianic acid. Their structures were determined based on spectroscopic methods. A preliminary study on leishmanicidal activity demonstrated that compounds 1, 2 and 6 were found to inhibit the growth of amastigote-like forms of Leishmania amazonensis without affecting mononuclear cells obtained from human peripheral blood

Serological secretome analysis of Corynebacterium pseudotuberculosis

Caseous lymphadenitis (CLA) is a chronic disease affecting small ruminants caused by Corynebacterium pseudotuberculosis and is responsible for significant economic losses. Previous studies have reported that a set of C. pseudotuberculosis secreted proteins react with sera from infected goats. Mapping of the secretome will shed light on the pathogenesis of CLA. We have hereby identified six immunoreactive secreted proteins of C. pseudotuberculosis by 2D Western blotting using sera from goats with CLA and characterized them by mass spectrometry. The information retrieved will support studies leading to the development of efficient vaccines and diagnostic kits

Future directions for the discovery of natural product-derived immunomodulating drugs

Drug discovery from natural sources is going through a renaissance, having spent many decades in the shadow of synthetic molecule drug discovery, despite the fact that natural product-derived compounds occupy a much greater chemical space than those created through synthetic chemistry methods. With this new era comes new possibilities, not least the novel targets that have emerged in recent times and the development of state-of-the-art technologies that can be applied to drug discovery from natural sources. Although progress has been made with some immunomodulating drugs, there remains a pressing need for new agents that can be used to treat the wide variety of conditions that arise from disruption, or over-activation, of the immune system; natural products may therefore be key in filling this gap. Recognising that, at present, there is no authoritative article that details the current state-of-the-art of the immunomodulatory activity of natural products, this in-depth review has arisen from a joint effort between the International Union of Basic and Clinical Pharmacology (IUPHAR) Natural Products and Immunopharmacology, with contributions from a Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation number of world-leading researchers in the field of natural product drug discovery, to provide a “position statement” on what natural products has to offer in the search for new immunomodulatory argents. To this end, we provide a historical look at previous discoveries of naturally occurring immunomodulators, present a picture of the current status of the field and provide insight into the future opportunities and challenges for the discovery of new drugs to treat immune-related diseases