Navegando por Palavras-chave "synthetic peptides"
Agora exibindo 1 - 4 de 4
Resultados por página
Opções de Ordenação
- ItemSomente MetadadadosDesign of inhibitors for human tissue kallikrein using non-natural aromatic and basic amino acids(Walter de Gruyter & Co, 2002-05-01) Pimenta, D. C.; Melo, R. L.; Caliendo, G.; Santagada, V; Fiorino, F.; Severino, B.; Nucci, G. de; Juliano, L.; Juliano, M. A.; Universidade Federal de São Paulo (UNIFESP); Univ Naples Federico II; Universidade de São Paulo (USP)We explored the unique substrate specificity of the primary S1 subsite of human urinary kallikrein (hK1), which accepts both Phe or Arg synthesizing and assaying peptides derived from PhenylacetylPheSer ArgEDDnp, a previously described inhibitor with analgesic and antiinflammatory activities [Emim et al., Br. J. Pharmacol. 130 (2000), 1099 1107]. Phe was substituted by amino acids containing larger aliphatic or aromatic side chains as well as by nonnatural basic amino acids, which were designed to combine a large hydrophobic and/or aromatic group with a positivelycharged group at their side chains. in general, all peptides with basic amino acids represented better inhibitors than those with hydrophobic amino acids. Furthermore, the S1 subsite specificity proved to be much more selective than the mere distinction between Phe and Arg, for minor differences in the side chains of the nonnatural amino acids resulted in major differences in the K-i values. Finally, we present a series of peptides that were assayed as competitive inhibitors for human tissue kallikrein that may lead to the development of novel peptides, which are both more potent and selective.
- ItemSomente MetadadadosIn vitro evaluation of leptin fragments activity on the ob receptor(Wiley-Blackwell, 2008-05-01) Oliveira, Vani Xavier de; Fazio, Marcos Antonio [UNIFESP]; Santos, Edson Lucas [UNIFESP]; Pesquero, Joao Bosco [UNIFESP]; Miranda, Antonio [UNIFESP]; Universidade Federal do ABC (UFABC); Universidade Federal de São Paulo (UNIFESP)In an attempt to identify regions in the leptin molecule responsible for its bioactivity, we tested six related-leptin peptide fragments denoted: Ae-hLEP(23-47)-NH(2) (I), Ac-hLEP(48-71)-NH(2) (II), Ac-hLEP(72-88)-NH(2) (III), Ac-hLEP(92-115)-NH(2) (IV), Ac-[Ser(117)]-hLEP(116-140)-NH(2) (V), Ac-hLEP(141-164)-NH(2) (VI) and their correspondent disulfide bridged dimer forms. the activity of the fragments was evaluated in comparision to leptin, by their ability to interact with leptin receptor using a cytosensor microphysiometer. Our results indicated that the fragments IV and V and [D-Leu(4)]-OB(3) and its human sequence analog were recognized by leptin receptor present in HP-75 cells, in agreement with the results obtained by other workers, validating that this region of the molecule contain the functional epitope of the leptin molecule. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.
- ItemSomente MetadadadosLeptin fragments induce Fos immunoreactivity in rat hypothalamus(Elsevier B.V., 2005-04-15) Oliveira, V. X.; Fazio, M. A.; Miranda, MTM; Silva, J. M. da; Bittencourt, J. C.; Elias, C. F.; Miranda, A.; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Leptin presents an important role in energy balance and neuroendocrine control in mammals. in an attempt to identify regions of the leptin molecule responsible for its bioactivity, we have synthesized six peptides based on the protein three-dimensional structure. Fragments were synthesized by the solid-phase methodology, purified by reverse-phase high-performance liquid chromatography (RP-HPLC), and characterized by liquid chromatography-electrospray ionization mass spectrometry (LC/ESI-MS). They were injected intravenously and their ability to induce Fos immunoreactivity (Fos-ir) in rat hypothalamus was compared with that of the recombinant human leptin and saline. Fragment Ac-[Ser(117)]Lep(116-140)-NH2 (V) induced Fos-ir in hypothalamic nuclei that express leptin receptor long form. No similar ability was observed for the other five fragments. To investigate whether Fos-ir was induced in the same neuronal group activated by leptin, we proceeded with a dual-label immunohistochemistry for cocaine- and amphetamine-regulated transcript (CART), a neuropeptide related to leptin action in rat hypothalamus. We found that Ac-[Ser(117)]Lep(116-140)-NH2 (V) differentially activates CART neurons through the rostrocaudal extension of the arcuate nucleus. These results suggest that this fragment acts in the same group of neurons that mediate leptin response. This approach may offer the basis for the development of leptin-related compounds, having potential application in human or veterinary medicine. (C) 2004 Published by Elsevier B.V.
- ItemSomente MetadadadosModeling the Trypanosoma cruzi Tc85-11 protein and mapping the laminin-binding site(Elsevier B.V., 2004-12-10) Marroquin-Quelopana, M.; Oyama, S.; Pertinhez, T. A.; Spisni, A.; Juliano, M. A.; Juliano, L.; Colli, W.; Alves, MJM; Universidade de São Paulo (USP); Lab Nacl Luz Sincrotron; Univ Parma; Universidade Federal de São Paulo (UNIFESP)Trypanosoma cruzi expresses a set of glycoproteins encoded by the gp85/trans-sialidase gene superfamily. in this report a structure model is proposed for a cloned member of the superfamily, the Tc85-11 protein. the structure consists of an N-terminus beta-propeller and a C-terminus beta-sandwich interconnected by an alpha-helix, the recombinant protein, corresponding to the N-domain (Tc85-N), binds to laminin in a selective manner. Six synthetic 20-mer peptides from the N-domain adhere onto the surface of LLC-MK2 cells and two of these peptides specifically inhibit the Tc85-N/laminin interaction, indicating that they are the laminin-binding sites of the molecule. Thus, Tc85-11 and other related members of the family appear to be good candidates to play an important role in T cruzi infection via a laminin mediated host-parasite interaction. (C) 2004 Elsevier Inc. All rights reserved.