Since aggressive therapy given early in the rheumatoid arthritis (RA) disease course has the greatest therapeutic potential, early diagnostic tests with both high specificity and sensitivity are desirable. Rheumatoid sera were found to contain antibodies against citrullinated peptides, which are considered to be highly specific markers of RA. In the present work several analogues of the alpha- and beta-chains of fibrin peptides containing different degrees of citrullination have been synthesized and analyzed by ELISA using 111 sera from RA patients. In addition, we have also investigated the synergistic effects of different presentation formats of the synthetic constructs. We have designed chimeric and cyclic peptides that bear different peptide sequences within the same molecule. Our results indicate that the synthesis of peptides bearing fibrinogen and filaggrin domains could be a robust method for the design of useful diagnostic strategies in RA.
The present work examines the relationship between the antimicrobial activity of novel arginine-based cationic surfactants and the physicochemical process involved in the perturbation of the cell membrane. To this end, the interaction of these surfactants with two biomembrane models, namely, 1,2-dipalmitoylsn-glycero-3-phosphocholine (DPPC) multilamellar lipid vesicles (MLVs) and monolayers of DPPC, 1,2dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] sodium salt (DPPG), and Escherichia coli total lipid extract, was investigated. For the sake of comparison, this study included two commercial antimicrobial agents, hexadecyltrimethylammonium bromide and chlorhexidine dihydrochloride. Changes in the thermotropic phase transition parameters of DPPC MLVs in the presence of the compounds were studied by differential scanning calorimetry analysis. The results show that variations in both the transition temperature (Tm) and the transition width at half-height of the heat absorption peak (∆T1/2) were consistent with the antimicrobial activity of the compounds. Penetration kinetics and compression isotherm studies performed with DPPC, DPPG, and E. coli total lipid extract monolayers indicated that both steric hindrance effects and electrostatic forces explained the antimicrobial agent-lipid interaction. Overall, in DPPC monolayers single-chain surfactants had the highest penetration capacity, whereas gemini surfactants were the most active in DPPG systems. The compression isotherms showed an expansion of the monolayers compared with that of pure lipids, indicating an insertion of the compounds into the lipid molecules. Owing to their cationic character, they are incorporated better into the negatively charged DPPG than into zwitterionic DPPC lipid monolayers.
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.
The use of synthetic peptides as HIV-1 inhibitors has been subject to research over recent years. Although the initial therapeutic attempts focused on HIV-coded enzymes, structural HIV proteins and, more specifically, the mechanisms that the virus uses to infect and replicate are now also considered therapeutic targets. The interest for viral fusion and entry inhibitors is growing significantly, given that they are applicable in combined therapies or when resistance to other antiretroviral drugs is seen and that they act before the virus enters the cell. The 124 synthetic sequences of the GBV-C E2 envelope protein have been obtained by SPPS. The interaction of certain GBV-C peptide sequences with the HIV-1 fusion peptide has been proven through the use of biophysical techniques. We also show how GBV-C E2 domains notably decrease cellular membrane fusion and interfere with the HIV-1 infectivity in a dose-dependent manner, highlighting their potential utility in future anti-HIV-1 therapies.
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