Polipéptido quimérico fibrina-filagrina citrulinado capaz de detectar los anticuerpos generados en la artritis reumatoide

Peer reviewedConsejo Superior de Investigaciones Científicas, Fundació Clinic per a la Recerca BiomédicaT3 Traducción de patente europe

Interaction of synthetic peptides corresponding to hepatitis G virus (HGV/GBV-C) E2 structural protein with phospholipid vesicles

11 pages, 7 figures, 2 tables.-- PMID: 15885095 [PubMed].-- Printed version published May 2005.The interaction with phospholipid bilayers of two synthetic peptides with sequences corresponding to a segment next to the native N-terminus and an internal region of the E2 structural hepatitis G virus (HGV/GBV-C) protein [E2(7–26) and E2(279–298), respectively] has been characterized. Both peptides are water soluble but associate spontaneously with bilayers, showing higher affinity for anionic than zwitterionic membranes. However, whereas the E2(7–26) peptide is hardly transferred at all from water to the membrane interface, the E2(279–298) peptide is able to penetrate into negatively charged bilayers remaining close to the lipid/water interface. The nonpolar environment clearly induces a structural transition in the E2(279–298) peptide from random coil to α-helix, which causes bilayer perturbations leading to vesicle permeabilization. The results indicate that this internal segment peptide sequence is involved in the fusion of HGV/GBV-C to membrane.This work was funded by grants BQU2003-05070-CO2-01/02 from the Ministerio de Ciencia y Tecnología (Spain) and a predoctoral grant awarded to C. L.Peer reviewe

Conjugation of cell-penetrating peptides with poly(Lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery

In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)- polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavail- ability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG- peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confrmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flur- biprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory effcacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment effciency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective preven- tion of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test-chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery.This work was supported by the Cooperation Research Program CSIC-CITMA and a project (MAT2011-26994) funded by the Spanish Ministry of Science and Technology. AV is a recipient of a PhD grant from the CSIC. The authors thank Nacho Pérez of the IQAC-CSIC for performing the cytotoxicity assays.Peer reviewe

Development of Peptide Targeted PLGA-PEGylated Nanoparticles Loading Licochalcone-A for Ocular Inflammation

Licochalcone-A is a natural compound with anti-inflammatory properties. However, it possesses low water solubility, making its application for the treatment of ocular inflammation difficult. To overcome this drawback, biodegradable nanoparticles incorporating Licochalcone-A have been developed. Additionally, to avoid fast clearance and increase cellular internalization into the ocular tissues, PLGA nanoparticles have been functionalized using PEG and cell penetrating peptides (Tet-1 and B6). To optimize the formulations, a factorial design was carried out and short-term stability of the nanoparticles was studied. Moreover, morphology was also observed by transmission electron microcopy and in vitro drug release was carried out. Ocular tolerance of the formulations was ensured in vitro and in vivo and anti-inflammatory therapeutic efficacy was also assessed. Surface functionalized nanoparticles loading Licochalcone-A were developed with an average size below 200 nm, a positive surface charge, and a monodisperse population. The formulations were non-irritant and showed a prolonged Licochalcone-A release. Despite the fact that both Licochalcone-A Tet-1 and B6 functionalized nanoparticles demonstrated to be suitable for the treatment of ocular inflammation, B6 targeted nanoparticles provided greater therapeutic efficacy in in vivo assays. Keywords: Licochalcone-A; nanoparticles; ocular inflammation; cell-penetrating peptides; PLG

Analysis of HIV-1 Fusion Peptide inhibition by synthetic peptides from E1 protein of GB virus C

The aim of this study was to identify proteins that could inhibit the activity of the peptide sequence representing the N-terminal of the surface protein gp41 of HIV, corresponding to the fusion peptide of the virus (HIV-1 FP). To do this we synthesized and studied 58 peptides corresponding to the envelope protein E1 of the hepatitis G virus (GBV-C). Five of the E1 synthetic peptides: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCL VALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18) and AQLVGELGSLYGPLSVSA (P22) were capable of inhibiting the leakage of vesicular contents caused by HIV-1 FP. A series of experiments were carried out to determine how these E1 peptides interact with HIV-1 FP. Our studies analyzed the interactions with and without the presence of lipid membranes. Isothermal titration calorimetry revealed that the binding of P7, P18 and P22 peptides to HIV-1 FP is strongly endothermic, and that binding is entropy-driven. Gibbs energy for the process indicates a spontaneous binding between E1 peptides and HIV-1 FP. Moreover, confocal microscopy of Giant Unilamellar Vesicles revealed that the disruption of the lipid bilayer by HIV-1 FP alone was inhibited by the presence of any of the five selected peptides. Our results highlight that these E1 synthetic peptides could be involved in preventing the entry of HIV-1 by binding to the HIV-1 FP. Therefore, the continued study into the interaction between GBV-C peptides and HIV-1 FP could lead to the development of new therapeutic agents for the treatment of AIDS

Study of the interaction of GB virus C/Hepatitis G virus fusion peptides belonging to the E2 protein with phospholipid Langmuir monolayers

In order to determine the ability of 1,2-dipalmitoyl phosphatidylcholine (DPPC) and 1,2-dioleoyl phosphatidylglycerol (DOPG) to host peptide sequences belonging to the E2 protein of GBV virus C/Hepatitis G virus, the behaviour of Langmuir monolayers formed by these phospholipids and E2 (12-26), E2 (354-363) and E2 (chimeric) peptide sequences was analysed from data of surface pressure (π) versus area per molecule (A) isotherms, compression modulus (Cs-1), excess Gibbs energy of mixing (ΔGexc) and total Gibbs energy of mixing (ΔGmix). Three different behaviours were observed. Mixed films of E2 (12-26) with DPPC or DOPC showed negative values for the excess thermodynamic functions, and thus attractive interactions between mixed films components are greater than in ideal films. Mixtures of E2 (354-363) with DPPC or DOPG, exhibited positive values of excess functions, evidencing weaker interactions in the mixed films in relation to those of pure components. Finally, positive and negative excess functions were observed in E2 (chimeric)/DPPC or DOPG mixed films, depending on their composition. In short, the interaction between the phospholipids used in this work as models of cell membranes and E2 peptides varies with the type of phospholipid and the nature of the peptide (size, bulky, hydrophobicity and electric charge)

Assessment of anti-malondialdehyde-acetaldehyde antibody frequencies in rheumatoid arthritis with new data from two independent cohorts, meta-analysis, and meta-regression

Autoantibodies are critical elements in RA pathogenesis and clinical assessment. The anti-malondialdehyde-acetaldehyde (anti-MAA) antibodies are potentially useful because of their claimed high sensitivity for all RA patients, including those lacking RF and anti-CCP antibodies. Therefore, we aimed to replicate these findings.The research done in Santiago was funded by Instituto de Salud Carlos III through the projects PI20/01268, PI17/01606 and RD21/0002/0003, co-funded by the European Union. L.R.-M. was supported by Xunta de Galicia (Spain) through a Gain pre-doctoral fellowship (IN606A-2017/015). The research in Barcelona was funded by the Spanish Ministry of Economy, Industry and Competitiveness and the European Regional Development Fund (Grant PID2021-122216OB-I00).Peer reviewe

Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity

Amyloid β-peptide (Aβ) misfolding into β-sheet structures triggers neurotoxicity inducing Alzheimer's disease (AD). Molecules able to reduce or to impair Aβ aggregation are highly relevant as possible AD treatments since they should protect against Aβ neurotoxicity. We have studied the effects of the interaction of dynorphins, a family of opioid neuropeptides, with Aβ40 the most abundant species of Aβ. Biophysical measurements indicate that Aβ40 interacts with Big Dynorphin (BigDyn), lowering the amount of hydrophobic aggregates, and slowing down the aggregation kinetics. As expected, we found that BigDyn protects against Aβ40 aggregates when studied in human neuroblastoma cells by cell survival assays. The cross-interaction between BigDyn and Aβ40 provides insight into the mechanism of amyloid pathophysiology and may open up new therapy possibilities.The authors would like to thank Mr. Jordi Pujols Pujol for skillful technical assistance in RP-HPLC experiments, and Mr. Mateo Calle Velásquez for skillful assistance in the docking process.Peer reviewe

Uso de péptidos de la proteína E1 del virus de la hepatitis G para inhibir la actividad del virus VIH

[EN] The invention relates to the use of peptides of the E1 protein of the hepatitis G virus in order to inhibit the activity of the HIV virus. More specifically, the invention relates to the use of at least one peptide, or a derivative of same, contained in the sequence of the E1 protein of the hepatitis G virus (GBV-C/HGV), capable of inhibiting the activity of the HIV virus, impeding or repressing the function and/or activity of the HIV virus (human immunodeficiency virus), in a temporary or permanent manner, or additionally capable of interacting with an amino acid sequence of glycoprotein gp41 of the HIV virus, for the production of a pharmaceutical composition. Said peptide can impede the inhibition of the function of the fragment of protein gp41 of the HIV virus, impede cell fusion or impede the replication of HIV in a host cell. In addition, the invention relates to the aforementioned pharmaceutical composition and to the method for the production thereof.[ES] La presente invención se refiere al uso de al menos un péptido, o derivado del mismo, contenido en la secuencia de la proteína E1 del virus de la hepatitis G (GBV-C/HGV), capaz de inhibir la actividad del virus VIH, impidiendo o reprimiendo la función y/o actividad del virus VIH (Virus de Inmunodeficiencia Humana), de forma transitoria o permanente, o además capaz de interaccionar con una secuencia aminoacídica de la glicoproteína gp41 del virus VIH, para la elaboración de una composición farmacéutica. Dicho péptido es capaz de impedir la inhibición de la función del fragmento de la proteína gp41 del virus VIH, impedir la fusión celular o impedir la replicación del VIH en una célula huésped. Asimismo la presente invención también se refiere a dicha composición farmacéutica y al método para su fabricación.Peer reviewedConsejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic

Synthetic peptides for the immunodiagnosis of human diseases

16 pages, 3 figures, 3 tables.-- PMID: 17346145 [PubMed].Synthetic peptides have been shown to be valuable tools for viral laboratory diagnosis and can provide uniform, chemically well-defined antigens for antibody analysis, reducing inter- and intra-assay variation.The main aim in the development of peptide-based diagnostic tests is to recognise specific antibodies induced by the whole viral proteins but using selected short fragments containing the most potent antigenic determinants. The success of this approach depends on the extent to which synthetic peptides are able to mimic the immunodominant epitopes of antigens. In recent years, synthetic peptides that mimic specific epitopes of infectious agents’ proteins have been used in diagnostic systems for various human diseases.The present review summarizes some of the drawbacks of the use of relatively short linear peptides as antigenic substrates and the subsequent chemical strategies developed in order to overcome the low peptide reactivity against specific antibodies. Moreover, it outlines the most significant bibliography published in the last five years which provides validated peptide based tests potentially useful for diagnosis of viral, bacterial, parasitic and autoimmune diseases.Ministerio de Ciencia e Innovación (proyecto CTQ2006-15396-CO2-01/BQU).Peer reviewe