Navegando por Palavras-chave "G-protein coupled receptor"

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    The Central Nervous System as Target for Antihypertensive Actions of a Proline-Rich Peptide from Bothrops jararaca Venom
    (Wiley-Blackwell, 2010-03-01) Lameu, Claudiana; Hayashi, Mirian Akemi Furuie [UNIFESP]; Guerreiro, Juliano R.; Oliveira, Eduardo F.; Lebrun, Ivo; Pontieri, Vera; Morais, Katia L. P.; Camargo, Antonio C. M.; Ulrich, Henning; Universidade de São Paulo (USP); Inst Butantan; Universidade Federal de São Paulo (UNIFESP)
    Pyroglutamyl proline-rich oligopeptides, present in the venom of the pit viper Bothrops jararaca (Bj-PROs), are the first described naturally occurring inhibitors of the angiotensin I-converting enzyme (ACE). the inhibition of ACE by the decapeptide Bj-PRO-10c (
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    The Ig V-H complementarity-determining region 3-containing Rb9 peptide, inhibits melanoma cells migration and invasion by interactions with Hsp90 and an adhesion G-protein coupled receptor
    (Elsevier Science Inc, 2016) Girola, Natalia [UNIFESP]; Matsuo, Alisson Leonardo [UNIFESP]; Figueiredo, Carlos Rogerio [UNIFESP]; Massaoka, Mariana Hiromi [UNIFESP]; Farias, Camyla Fernandez de [UNIFESP]; Arruda, Denise C.; Azevedo, Ricardo A.; Monteiro, Hugo Pequeno [UNIFESP]; Resende-Lara, Pedro T.; Cunha, Rodrigo L. O. R.; Polonelli, Luciano; Travassos, Luiz Rodolpho [UNIFESP]
    The present work aims at investigating the mechanism of action of the Rb9 peptide, which contains the VHCDR 3 sequence of anti-sodium-dependent phosphate transport protein 2B (NaPi2B) monoclonal antibody RebMab200 and displayed antitumor properties. Short peptides corresponding to the hyper variable complementarity-determining regions (CDRs) of immunoglobulins have been associated with antimicrobial, antiviral, immunomodulatory and antitumor activities regardless of the specificity of the antibody. We have shown that the CDR derived peptide Rb9 induced substrate hyperadherence, inhibition of cell migration and matrix invasion in melanoma and other tumor cell lines. Rb9 also inhibited metastasis of murine melanoma in a syngeneic mouse model. We found that Rb9 binds to and interferes with Hsp90 chaperone activity causing attenuation of FAK-Src signaling and downregulation of active Rac1 in B16F10-Next melanoma cells. The peptide also bound to an adhesion G-protein coupled receptor, triggering a concentration-dependent synthesis of cAMP and activation of PKA and VASP signaling as well as IP-3 dependent Ca2+ release. Hsp90 is highly expressed on the cell surface of melanoma cells, and synthetic agents that target Hsp90 are promising cancer therapeutic drugs. Based on their remarkable antitumor effects, the CDR-H3-derived peptides from RebMab200, and particularly the highly soluble and stable Rb9, are novel candidates to be further studied as potential antitumor drugs, selectively acting on cancer cell motility and invasion. (C) 2016 Elsevier Inc. All rights reserved.
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    Trifluoroethanol and binding to model membranes stabilize a predicted turn in a peptide corresponding to the first extracellular loop of the angiotensin II AT(1A) receptor
    (Wiley-Blackwell, 2002-10-05) Salinas, R. K.; Shida, C. S.; Pertinhez, T. A.; Spisni, A.; Nakaie, C. R.; Paiva, ACM; Schreier, S.; Universidade de São Paulo (USP); Natl Lab Synchrotron Light; Universidade Federal de São Paulo (UNIFESP)
    Homology modeling of the angiotensin H AT(1A) receptor based oil rhodopsin's crystal structure has assigned the 92-100 (YRWPFGNHL) sequence of the receptor to its first extracellular loop. Solution and membrane-bound conformational properties of a peptide containing this sequence (EL1) were examined by CD, fluorescence, and H-1-NMR. CD spectra in aqueous solution revealed an equilibrium between less organized and folded conformers. NMR spectra indicated the coexistence of trans and cis isomers of the Trp(3)-Pro(4) bond. A positive band at 226 urn in the CD spectra suggested aromatic ring stacking, modulated by EL1's ionization degree. CD spectra showed that trifluoroethanol (TFE), or binding to detergent micelles and phospholipid bilayers, shifted the equilibrium toward conformers with higher secondary structure content. Different media gave rise to spectra suggestive of different beta-turns. Chemical shaft changes in the NMR spectra corroborated the stabilization of different conformations. Thus, environments of lower polarity or binding to interfaces probably favored the formation of hydrogen bonds, stabilizing beta-turns, predicted for this sequence in the whole receptor. Increases in Trp(3) fluorescence intensity and anisotropy, blue shifts of the maximum emission wavelength, and pK changes also evinced the interaction between EL1 and model membranes. Binding was seen to depend on both hydrophobic and electrostatic interactions, as well cis lipid phase packing. Studies with water-soluble and membrane-bound fluorescence quenchers demonstrated that Trp(3) is located close to the water-membrane interface. the results are discussed with regard to possible implications in receptor folding and function. (C) 2002 Wiley Periodicals, Inc. Biopolymers 65: 21-31, 2002.