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Mar. Drugs 2017, 15(4), 123; doi:10.3390/md15040123

Identification of Tight-Binding Plasmepsin II and Falcipain 2 Inhibitors in Aqueous Extracts of Marine Invertebrates by the Combination of Enzymatic and Interaction-Based Assays

1
Centro de Estudio de Proteínas, 25 # 455 entre J e I. Facultad de Biología, Universidad de la Habana, 10400 La Habana, Cuba
2
Coordinación Red CYTED-PROMAL (210RT0398), Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria, Universidad Nacional de la Plata, 1900 La Plata, Argentina
3
Institut de Biotecnologia i de Biomedicina and Departament de Bioquímica i de Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona), Spain
Both authors contributed equally to this work.
Current Address: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad #2001, Col. Chamilpa, 62210 Cuernavaca, Morelos, Mexico.
*
Authors to whom correspondence should be addressed.
Academic Editor: Sadanandan E. Velu
Received: 28 February 2017 / Revised: 16 April 2017 / Accepted: 18 April 2017 / Published: 21 April 2017
(This article belongs to the Special Issue Enzyme Inhibitors of Marine Origin)
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Abstract

Natural products from marine origin constitute a very promising and underexplored source of interesting compounds for modern biotechnological and pharmaceutical industries. However, their evaluation is quite challenging and requires specifically designed assays to reliably identify the compounds of interest in a highly heterogeneous and interfering context. In the present study, we describe a general strategy for the confident identification of tight-binding protease inhibitors in the aqueous extracts of 62 Cuban marine invertebrates, using Plasmodium falciparum hemoglobinases Plasmepsin II and Falcipain 2 as model enzymes. To this end, we first developed a screening strategy that combined enzymatic with interaction-based assays and then validated screening conditions using five reference extracts. Interferences were evaluated and minimized. The results from the massive screening of such extracts, the validation of several hits by a variety of interaction-based assays and the purification and functional characterization of PhPI, a multifunctional and reversible tight-binding inhibitor for Plasmepsin II and Falcipain 2 from the gorgonian Plexaura homomalla, are presented. View Full-Text
Keywords: tight-binding protease inhibitor; combined screening strategy; Plasmepsin II; Falcipain 2; Plasmodium falciparum tight-binding protease inhibitor; combined screening strategy; Plasmepsin II; Falcipain 2; Plasmodium falciparum
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MDPI and ACS Style

Salas-Sarduy, E.; Guerra, Y.; Covaleda Cortés, G.; Avilés, F.X.; Chávez Planes, M.A. Identification of Tight-Binding Plasmepsin II and Falcipain 2 Inhibitors in Aqueous Extracts of Marine Invertebrates by the Combination of Enzymatic and Interaction-Based Assays. Mar. Drugs 2017, 15, 123.

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