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
Salas-Sarduy, Emir (Universidad de La Habana (La Havana, Cuba). Centro de Estudio de Proteínas)
Guerra, Yasel (Universidad de La Habana (La Havana, Cuba). Centro de Estudio de Proteínas)
Covaleda Cortés, Giovanni (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Avilés, Francesc Xavier (Francesc Xavier) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Chávez Planes, María A. (Universidad de La Habana (La Havana, Cuba). Centro de Estudio de Proteínas)

Date:	2017
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.
Grants:	Ministerio de Economía y Competitividad BIO2016-78057-R Ministerio de Economía y Competitividad BIO2013-44973-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1658
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Tight-binding protease inhibitor ; Combined screening strategy ; Plasmepsin II ; Falcipain 2 ; Plasmodium falciparum
Published in:	Marine drugs, Vol. 15, Issue 4 (April 2017) , ISSN 1660-3397

DOI: 10.3390/md15040123
PMID: 28430158

26 p, 5.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles