Teresa Tarragó

Institute for Research in Biomedicine

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i-10 index

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Ernest Giralt

Universitat de Barcelona

Roger Prades

Barcelona Biomedical Research Park

Meritxell Teixidò

Institute for Research in Biomedicine

Eduard Sabidó

Centre for Genomic Regulation

Laura Mendieta

Institute for Research in Biomedicine

Nessim Kichik

King's College London

Abraham López

Technical University of Munich

Margarida Gairí

Universitat de Barcelona

J. Javier Meana

Centro de Investigación Biomédica en Red de Salud Mental

Sergio Madurga

Universitat de Barcelona

Cooperative Institutions

Universitat de Barcelona

Institute for Research in Biomedicine

Instituto de Salud Carlos III

Consejo Superior de Investigaciones Científicas

Barcelona Biomedical Research Park

Centro de Investigación Biomédica en Red

Universitat Autònoma de Barcelona

Hospital de Sant Pau

FC Barcelona

Amsterdam Neuroscience

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Exploration of the One-Bead One-Compound Methodology for the Design of Prolyl Oligopeptidase Substrates

PLoS ONE (2009)

Gemma Comellas Zuzanna Kaczmarska Teresa Tarragó Meritxell Teixidò Ernest Giralt

Here we describe the design, synthesis and evaluation of the first solid-phase substrates for prolyl oligopeptidase (POP), a cytosolic serine peptidase associated with schizophrenia, bipolar affective disorder and related neuropsychiatric disorders. This study seeks to contribute to the future design of a one-bead one-compound (OBOC) peptide library of POP substrates, based on an intramolecular energy transfer substrate. Unexpectedly, the enzymatic evaluation of the substrates attached on solid-phase by means of the HMBA linker were cleaved through the ester bond, thereby suggesting an unknown esterase activity of POP, in addition to its known peptidase activity. By performing multiple activity assays, we have confirmed the esterase activity of this enzyme and its capacity to process the substrates on solid-phase. Finally, we tested a new linker, compatible with both the solid-phase peptide-synthesis used and the enzymatic assay, for application in the future design of an OBOC library.

Oligopeptidase

Linker

Solid-Phase Synthesis

Rational design

10.1371/journal.pone.0006222

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Citations (9)

Small Peptide Inhibitors Disrupt a High-Affinity Interaction between Cytoplasmic Dynein and a Viral Cargo Protein

Journal of Virology (2010)

Bruno Hernáez Teresa Tarragó Ernest Giralt José M. Escribano Covadonga Alonso

ABSTRACT Several viruses target the microtubular motor system in early stages of the viral life cycle. African swine fever virus (ASFV) protein p54 hijacks the microtubule-dependent transport by interaction with a dynein light chain (DYNLL1/DLC8). This was shown to be a high-affinity interaction, and the residues gradually disappearing were mapped on DLC8 to define a putative p54 binding surface by nuclear magnetic resonance (NMR) spectroscopy. The potential of short peptides targeting the binding domain to disrupt this high-affinity protein-protein interaction was assayed, and a short peptide sequence was shown to bind and compete with viral protein binding to dynein. Given the complexity and number of proteins involved in cellular transport, the prevention of this viral-DLC8 interaction might not be relevant for successful viral infection. Thus, we tested the capacity of these peptides to interfere with viral infection by disrupting dynein interaction with viral p54. Using this approach, we report on short peptides that inhibit viral growth.

Dynactin

Viral structural protein

Viral protein

Viral life cycle

10.1128/jvi.01168-10

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Citations (42)

Location of Disulfide bonds in mature α‐L;‐fucosidase from pea

Journal of Peptide Science (2001)

Anna Codina Marta Vilaseca Teresa Tarragó Irene Fernández Dolors Ludevid

Abstract Fuc‐9 is the mature form of a vacuolar α‐ L ;‐fucosidase enzyme which seems to play an important role in plant growth regulation. Fuc‐9 is a 202‐residue protein containing five Cys residues located at positions 64, 109, 127, 162 and 169. In this study, the disulfide structure of Fuc‐9 was determined by MALDI‐TOF mass spectrometry (MS), with minimal clean‐up of the samples and at a nanomolar scale. Two strategies, based on a specific chemical cleavage (with 2‐nitro‐5‐thiocyanobenzoic acid and alkaline conditions) at the Cys residues and modification of Cys residues by acrylamide/deuterium labeled acrylamide alkylation, were used. Using these methods, the disulfide pairings Cys64‐Cys109 and Cys162‐Cys169 could be established. The advantages and limitations of our experimental approach are discussed. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.

Residue (chemistry)

Cleavage (geology)

Disulfide Linkage

Posttranslational modification

10.1002/psc.323

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Citations (9)

Baicalin, a prodrug able to reach the CNS, is a prolyl oligopeptidase inhibitor

Bioorganic & Medicinal Chemistry (2008)

Teresa Tarragó Nessim Kichik Birgit Claasen Roger Prades Meritxell Teixidò

Baicalin

Oligopeptidase

Baicalein

Aglycone

10.1016/j.bmc.2008.04.067

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Citations (87)

Towards the identification of unknown neuropeptide precursor-processing enzymes: Design and synthesis of a new family of dipeptidyl phosphonate activity probes for substrate-based protease identification

Bioorganic & Medicinal Chemistry (2010)

Eduard Sabidó Teresa Tarragó Ernest Giralt

Proteolysis

Phosphonate

Proteome

10.1016/j.bmc.2010.09.066

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Citations (13)

Applications and future of ion mobility mass spectrometry in structural biology

New Journal of Chemistry (2013)

Abraham López Teresa Tarragó Marta Vilaseca Ernest Giralt

Ion mobility coupled to mass spectrometry (IMMS) is a technique that simultaneously separates gaseous ions on the basis of their mass, shape and size. The continuous advances in native mass spectrometry applied to IMMS have prompted its application in the structural study of biomolecules. Hence, challenging systems in terms of molecular size, complexity and heterogeneity can be transferred to the gas phase and their structural properties can be analyzed. Although IMMS is a low resolution technique, in silico theoretical models or simulations can provide valuable microscopic information about the structure, dynamics and population of the species. Given these unprecedented advantages of IMMS, this emerging method is becoming an established, reliable and versatile tool for structural biology.

Ion-mobility spectrometry

Biomolecule

10.1039/c3nj41051j

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Citations (16)

Chemical Composition and Inhibitory Effects of Hypericum brasiliense and H. connatum on Prolyl Oligopeptidase and Acetylcholinesterase Activities

Medicinal Chemistry (2016)

Maura Z. Santos Ionara I. Dalcol Luciana Adolpho Meritxell Teixidò Teresa Tarragó

The genus Hypericum (family Clusiaceae) comprises various species that are used in traditional medicine, such as wound healing, antidepressant, and anticancer agents.The aim of this study was to evaluate the inhibitory capacity of extracts and fractions from two Hypericum species used in the Brazilian folk medicine (H. brasiliense and H. connatum) against the enzymes prolyl oligopeptidase (POP), dipeptidyl peptidase-IV (DPP-IV), and acetylcholinesterase (AChE), as well as to identify their main active constituents.Dried aerial parts of H. connatum and H. brasiliense were subjected to extraction with 8:2 methanol-H2O. Each hydroalcoholic extract was fractioned resulting in ethyl acetate and aqueous fractions. The activity of POP, DPP-IV and AChE was determined in vitro in 96-well microplates.The main components identified in the plant extracts were chlorogenic acid (1), quercitrin (2), rutin (3), quercetin (4), and isoquercitrin (5). Hydroalcoholic extracts, ethyl acetate and aqueous fractions showed high POP inhibitory activity with IC50 values of 2.6 to 3.7 µg/mL. AChE and DPP-IV inhibitory effects were very low for all extracts and substances.Chlorogenic acid (1) and quercetin (4) were the main constituent responsible for the activity observed against POP. Parallel artificial membrane permeability assay of ethyl acetate fractions of both species showed that the metabolite that can effectively pass through the lipid membrane is 4, the aglycone form of 2, 3 and 5.

Quercitrin

Stigmasterol

Chlorogenic Acid

Oligopeptidase

Ursolic acid

Hyperforin

Aglycone

Hypericum

Hyperoside

IC50

10.2174/1573406411666151026121845

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Citations (4)

Simultaneous ¹⁹F NMR Screening of Prolyl Oligopeptidase and Dipeptidyl Peptidase IV Inhibitors

ChemBioChem (2010)

Nessim Kichik Teresa Tarragó Ernest Giralt

Prolyl oligopeptidase (POP) and dipeptidyl peptidase IV (DPP IV) are serine proteases that belong to the same family of enzymes. These peptidases are relevant because of their association with the pathophysiology of serious illnesses, such as type 2 diabetes (DPP IV), and those related to cognitive disorders (POP). Several NMR-based screening methods are being used to find and validate new hit scaffolds. In particular, (19)F NMR-based screening methods have proven to be powerful tools for the discovery and development of new inhibitors. Here we present an accurate and reliable (19)F NMR-based simultaneous assay that is used to screen for new selective POP and DPP IV inhibitors in compound mixtures. This activity assay consists of the simultaneous performance of POP and DPP-IV (19)F NMR activity assays in the presence of their fluorine-containing substrates. Furthermore, the assays were conducted in the presence of 0.01 % v/v of Triton X-100, which is a detergent that disrupts micelle formation, thereby preventing unspecific aggregate-based inhibition. Finally, this (19)F NMR methodology was applied to screen for ligands in plant extracts. Our results indicate that this method allows the simultaneous and accurate identification of selective POP and DPP IV inhibitors in these compound mixtures.

Oligopeptidase

Dipeptidyl peptidase

10.1002/cbic.201000019

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Citations (16)

ChemInform Abstract: Applications and Future of Ion Mobility Mass Spectrometry in Structural Biology

ChemInform (2013)

Abraham López Teresa Tarragó Marta Vilaseca Ernest Giralt

Abstract Review: 63 refs.

Ion-mobility spectrometry

10.1002/chin.201339280

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Citations (0)

Low molecular weight inhibitors of Prolyl Oligopeptidase: a review of compounds patented from 2003 to 2010

Expert Opinion on Therapeutic Patents (2011)

Abraham López Teresa Tarragó Ernest Giralt

Introduction: Prolyl Oligopeptidase (POP) is a serine peptidase that cleaves post-proline bonds in short peptides. Besides the direct hydrolytic regulation function over peptides, neuropeptides and peptide hormones, POP is probably involved in the regulation of the inositol pathway and participates in protein-protein interactions. Experimental data show that POP inhibitors have neuroprotective, anti-amnesic and cognition-enhancing properties. These compounds are considered therapeutic agents of interest for the treatment of cognitive deficits related to neuropsychiatric and neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Recent findings pointed to the involvement of POP in angiogenesis, although the exact mechanism is still under study. Areas covered: This review comprises patents and patent applications involving POP inhibitors patented between 2003 and 2010, classified as peptidomimetics, heteroaryl ketones and alkaloids. The binding processes and the mechanisms of inhibition of these inhibitors are also discussed, together with their in vivo effects. Expert opinion: The major part of the repertory of POP inhibitors derived from systematical modification of the canonical compound benzyloxycarbonyl-prolyl-prolinal (ZPP). Nevertheless, only two of them have progressed into the clinical trials. One possible reason for this failure is the lack of studies concerning pharmacodynamics, pharmacokinetics and toxicity, together with the absence of suitable animal models. Moreover, POP is still not a well-defined therapeutic target. Further studies are required for the elucidation of the biological role of POP and to validate the therapeutic action of inhibitors in cognitive processes. In contrast, the involvement of POP in protein-protein interactions together with the recent evidences in angiogenesis opens alternative approaches to the traditional active site-directed inhibitors, as well as new therapeutic applications.

Oligopeptidase

Peptidomimetic

10.1517/13543776.2011.577416

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Citations (32)