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      Organismos marinhos como fonte de novos fármacos: histórico & perspectivas Translated title: Marine organisms as a source of new pharmaceuticals: history and perspectives

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          Translated abstract

          Though sharing only a short part on the natural products timeline, the studies on marine products has already handed in four new drugs to the clinical arsenal and brought up a long and promising list of unique molecules to pre-clinical and clinical trials. Thus, as the available analytical resources improve and the interest of large pharmaceutical companies arises, medical use of marine products has definitely become a reality.

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          Most cited references64

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          Designing chemically modified oligonucleotides for targeted gene silencing.

          Glen F. Deleavey, Masad J. Damha (2012)
          Oligonucleotides (ONs), and their chemically modified mimics, are now routinely used in the laboratory as a means to control the expression of fundamentally interesting or therapeutically relevant genes. ONs are also under active investigation in the clinic, with many expressing cautious optimism that at least some ON-based therapies will succeed in the coming years. In this review, we will discuss several classes of ONs used for controlling gene expression, with an emphasis on antisense ONs (AONs), small interfering RNAs (siRNAs), and microRNA-targeting ONs (anti-miRNAs). This review provides a current and detailed account of ON chemical modification strategies for the optimization of biological activity and therapeutic application, while clarifying the biological pathways, chemical properties, benefits, and limitations of oligonucleotide analogs used in nucleic acids research. Copyright © 2012 Elsevier Ltd. All rights reserved.
          Article 0 comments Cited 175 times – based on 0 reviews     Review now
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            Mechanism for the endocytosis of spherical nucleic acid nanoparticle conjugates.

            Chung Hang J Choi, Liangliang Hao, Suguna P. Narayan … (2013)
            Intracellular delivery of nucleic acids as gene regulation agents typically requires the use of cationic carriers or viral vectors, yet issues related to cellular toxicity or immune responses hamper their attractiveness as therapeutic candidates. The discovery that spherical nucleic acids (SNAs), polyanionic structures comprised of densely packed, highly oriented oligonucleotides covalently attached to the surface of nanoparticles, can effectively enter more than 50 different cell types presents a potential strategy for overcoming the limitations of conventional transfection agents. Unfortunately, little is known about the mechanism of endocytosis of SNAs, including the pathway of entry and specific proteins involved. Here, we demonstrate that the rapid cellular uptake kinetics and intracellular transport of SNAs stem from the arrangement of oligonucleotides into a 3D architecture, which supports their targeting of class A scavenger receptors and endocytosis via a lipid-raft-dependent, caveolae-mediated pathway. These results reinforce the notion that SNAs can serve as therapeutic payloads and targeting structures to engage biological pathways not readily accessible with linear oligonucleotides.
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              Developing irreversible inhibitors of the protein kinase cysteinome.

              Qingsong Liu, Yogesh Sabnis, Zheng Zhao … (2013)
              Protein kinases are a large family of approximately 530 highly conserved enzymes that transfer a γ-phosphate group from ATP to a variety of amino acid residues, such as tyrosine, serine, and threonine, that serves as a ubiquitous mechanism for cellular signal transduction. The clinical success of a number of kinase-directed drugs and the frequent observation of disease causing mutations in protein kinases suggest that a large number of kinases may represent therapeutically relevant targets. To date, the majority of clinical and preclinical kinase inhibitors are ATP competitive, noncovalent inhibitors that achieve selectivity through recognition of unique features of particular protein kinases. Recently, there has been renewed interest in the development of irreversible inhibitors that form covalent bonds with cysteine or other nucleophilic residues in the ATP-binding pocket. Irreversible kinase inhibitors have a number of potential advantages including prolonged pharmacodynamics, suitability for rational design, high potency, and ability to validate pharmacological specificity through mutation of the reactive cysteine residue. Here, we review recent efforts to develop cysteine-targeted irreversible protein kinase inhibitors and discuss their modes of recognizing the ATP-binding pocket and their biological activity profiles. In addition, we provided an informatics assessment of the potential "kinase cysteinome" and discuss strategies for the efficient development of new covalent inhibitors. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Journal ID (publisher-id): qn
                Title: Química Nova
                Abbreviated Title: Quím. Nova
                Publisher: Sociedade Brasileira de Química (São Paulo, SP, Brazil )
                ISSN (Print): 0100-4042
                ISSN (Electronic): 1678-7064
                Publication date (Print and electronic): 2009
                Volume: 32
                Issue: 3
                Pages: 703-716
                Affiliations
                [02] Niterói RJ orgnameUniversidade Federal Fluminense orgdiv1Instituto de Química Brasil
                [01] Fortaleza CE orgnameUniversidade Federal do Ceará orgdiv1Instituto de Ciências do Mar orgdiv2Laboratório de Oncologia Experimental Brasil
                Article
                Publisher ID: S0100-40422009000300014 Publisher ID: S0100-4042(09)03200300014
                DOI: 10.1590/S0100-40422009000300014
                SO-VID: 9619355d-f86d-492b-a8ef-d2e9999616e2
                License:

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                Date received : 15 January 2009
                Date accepted : 11 March 2009
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 189, Pages: 14
                Product

                SciELO Brazil

                Categories
                Subject: Artigo

                Keywords: marine drugs,marine biotechnology,natural products
                Data availability:
                Keywords: marine drugs, marine biotechnology, natural products

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