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Synthesis, kinetic studies and applications of substrates and inhibitors for proteolytic enzymes

Grant number: 12/50191-4
Support type:Research Projects - Thematic Grants
Duration: December 01, 2012 - November 30, 2018
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Principal researcher:Maria Aparecida Juliano
Grantee:Maria Aparecida Juliano
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated grant(s):18/13588-0 - Multi - user equipment approved in grant 2012/50191-4: mass spectrometer impact II - Bruker, AP.EMU
Associated scholarship(s):15/01829-4 - Human Tissue Kallikrein (KLK1) and human plasma kallikrein on metabolism of semaphorins and neurotrophins, BP.PD
14/18877-9 - Proteolytic enzymes in skin physiology and pathophysiology, BP.PD
14/18451-1 - Leptospira spp. strains database implemention by MALDI-TOF-MS and activity analysis of their secreted proteases, BP.IC
+ associated scholarships 13/21455-6 - Applied study will bioanalytical search profile blood plasma amino acid carriers Syndrome Cri-Du-Chat, BP.MS
13/07763-0 - Studies of Radical Acetylation of Proteins Using Proteomics Tools, BP.DR
13/12106-8 - Screening and characterization of serine carboxyl peptidases and glutamic peptidases in bacteria isolated from the composting operation at the São Paulo Zoo Park, BP.PD
13/06654-2 - Synthesis and functionalization of mesoporous silicas aiming application bioanalytical, BP.IC
11/20941-9 - DEVELOPMENT AND USE OF FLUORESCENCE TECHNIQUES FOR THE STUDY OF PROTEIN CONFORMATIONAL CHANGES, BP.PD - associated scholarships

Abstract

Considerable progress in the study of proteases was based on the development of synthetic peptides, which resulted in the chromogenic and fluorescent substrates. Quenched fluorescent peptides based on the transfer of energy by resonance of a fluorescent to a quancher group was the more recent and significant progress in the field that we are involve since 1990's. The synthesis of these FRET (Fluorescence Resonance Energy Transfer) peptides in solid phase linked to flexible resins and in systems of parallel synthesis allowed us to study the substrate specificity of several proteases by systematic variations in all positions of peptides with up to 10 amino acids in length. The project presented here is based on the development of modern techniques of organic synthesis and protein biochemistry for study of proteases involved in physiological and pathological processes. The proposals of this project are: Synthesis and assays with proteases of FRET peptide libraries in solid phase and in solution. Synthesis of protease inhibitors using non-natural amino acids. Assays as protease inhibitors of tellurium organic compounds and nitroolefins, particularly the cysteine proteases. Systematic studies will be done with human kallikreins, Plamodium and Leishmania proteases, processing peptidases and oligopeptidases. Virus, fungi and bactéria proteases were also included. (AU)

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Scientific publications (29)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ORLANDI-MATTOS, PAULO EDUARDO; AGUIAR, RODRIGO BARBOSA; VAZ JUNIOR, ITABAJARA DA SILVA; MORAES, JANE ZVEITER; DE ARAUJO CARLINI, ELISALDO LUIZ; JULIANO, MARIA APARECIDA; JULIANO, LUIZ. Enkephalin related peptides are released from jejunum wall by orally ingested bromelain. Peptides, v. 115, p. 32-42, . (12/50191-4)
CARVALHAES, CECILIA GODOY; RAMOS, ANA CAROLINA; GONCALVES DE OLIVEIRA, LILIAN CAROLINE; JULIANO, MARIA APARECIDA; GALES, ANA CRISTINA. Rapid detection of ceftazidime/avibactam resistance by MALDI-TOF MS. Journal of Antimicrobial Chemotherapy, v. 73, n. 9, p. 2579-2582, . (12/50191-4)
OKAMOTO, DEBORA N.; KONDO, MARCIA Y.; OLIVEIRA, LILIAN C. G.; HONORATO, RODRIGO V.; ZANPHORLIN, LETICIA M.; CORONADO, MONIKA A.; ARAUJO, MARIANA S.; DA MOTTA, GUACYARA; VERONEZ, CAMILA L.; ANDRADE, SHEILA S.; et al. P-I class metalloproteinase from Bothrops moojeni venom is a post-proline cleaving peptidase with kininogenase activity: Insights into substrate selectivity and kinetic behavior. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1844, n. 3, p. 545-552, . (12/50191-4)
REISS-PISTILLI, MARIA L. V.; SCHUPPAN, DETLEF; BARROSO, MADALENA M. S.; ASSUNCAO-MIRANDA, IRANAIA; FARIAS, SHIRLEY; LERY, LETICIA; BAUER, MICHAEL; JULIANO, LUIZ; JULIANO, MARIA A.; COELHO-SAMPAIO, TATIANA. An extracellular proteasome releases endostatin from human collagen XVIII. ANGIOGENESIS, v. 20, n. 1, p. 125-137, . (12/50191-4)
STEINBERGER, JUTTA; GRISHKOVSKAYA, IRINA; CENCIC, REGINA; JULIANO, LUIZ; JULIANO, MARIA A.; SKERN, TIM. Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage. VIROLOGY, v. 468, p. 397-408, . (12/50191-4)
OLIVEIRA, JULIANA R.; BERTOLIN, THIAGO C.; ANDRADE, DOUGLAS; OLIVEIRA, LILIAN C. G.; KONDO, MARCIA Y.; SANTOS, JORGE A. N.; BLABER, MICHAEL; JULIANO, LUIZ; SEVERINO, BEATRICE; CALIENDO, GIUSEPPE; et al. Specificity studies on Kallikrein-related peptidase 7 (KLK7) and effects of osmolytes and glycosaminoglycans on its peptidase activity. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1854, n. 1, p. 73-83, . (12/50191-4)
ABREU, AFONSO G.; FRAGA, TATIANA R.; GRANADOS MARTINEZ, ADRIANA P.; KONDO, MARCIA Y.; JULIANO, MARIA A.; JULIANO, LUIZ; NAVARRO-GARCIA, FERNANDO; ISAAC, LOURDES; BARBOSA, ANGELA S.; ELIAS, WALDIR P.. The Serine Protease Pic From Enteroaggregative Escherichia coli Mediates Immune Evasion by the Direct Cleavage of Complement Proteins. Journal of Infectious Diseases, v. 212, n. 1, p. 106-115, . (11/14103-0, 10/50043-0, 12/50191-4)
MARCONDES, M. F. M.; ALVES, F. M.; ASSIS, D. M.; HIRATA, I. Y.; JULIANO, L.; OLIVEIRA, V.; JULIANO, M. A.. Substrate specificity of mitochondrial intermediate peptidase analysed by a support-bound peptide library. FEBS OPEN BIO, v. 5, p. 429-436, . (14/00661-0, 12/50191-4, 11/20941-9)
JOCELINO GOMES DE LACERDA, JOSE THALLES; RODRIGUES E LACERDA, RODRIGO; ASSUNCAO, NILSON ANTONIO; TASHIMA, ALEXANDRE KEIJI; JULIANO, MARIA APARECIDA; DOS SANTOS, JR., GILBERTO ALVES; DE SOUZA, MILENY DOS SANTOS; BATISTA, JACINTO DE LUNA; ROSSI, CARLOS EDUARDO; DE ALMEIDA GADELHA, CARLOS ALBERTO; et al. New insights into lectin from Abelmoschus esculentus seeds as a Kunitz-type inhibitor and its toxic effects on Ceratitis capitata and root-knot nematodes Meloidogyne spp.. Process Biochemistry, v. 63, p. 96-104, . (12/19321-9, 12/02514-9, 12/50191-4)
NANI, JOAO V.; LEE, RICHARD S.; YONAMINE, CAMILA M.; SANT'ANNA, OSVALDO A.; JULIANO, MARIA A.; GADELHA, ARY; MARI, JAIR J.; HAYASHI, MIRIAN A. F.. Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics. SCIENTIFIC REPORTS, v. 10, n. 1, . (19/09207-3, 17/02413-1, 12/50191-4, 13/13392-4)
SONG, EUN SUK; JANG, HYEIN; GUO, HOU-FU; JULIANO, MARIA A.; JULIANO, LUIZ; MORRIS, ANDREW J.; GALPERIN, EMILIA; RODGERS, DAVID W.; HERSH, LOUIS B.. Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 114, n. 14, p. E2826-E2835, . (12/50191-4)
DO NASCIMENTO, EDILZA SILVA; ANAYA, KATYA; DE OLIVEIRA, JULIA MARIANO CAJU; DE LACERDA, JOSE THALLES JOCELINO GOMES; MILLER, MICHAEL EDWARD; DIAS, MERIELLEN; MENDES, MARIA ANITA; PALLONE, JULIANA DE AZEVEDO LIMA; ARNS, CLARICE WEIS; JULIANO, MARIA APARECIDA; et al. Identification of bioactive peptides released from in vitro gastrointestinal digestion of yam proteins (Dioscorea cayennensis). Food Research International, v. 143, . (12/50191-4, 18/13588-0)
GILIO, JOYCE M.; MARCONDES, MARCELO F.; FERRARI, DEBORA; JULIANO, MARIA A.; JULIANO, LUIZ; OLIVEIRA, VITOR; MACHADO, MAURICIO F. M.. Processing of metacaspase 2 from Trypanosoma brucei (TbMCA2) broadens its substrate specificity. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1865, n. 4, p. 388-394, . (15/11190-0, 14/20847-0, 12/50191-4)
SILVA, ROBERTA N.; OLIVEIRA, LILIAN C. G.; PARISE, CAROLINA B.; OLIVEIRA, JULIANA R.; SEVERINO, BEATRICE; CORVINO, ANGELA; DI VAIO, PAOLA; TEMUSSI, PIERO A.; CALIENDO, GIUSEPPE; SANTAGADA, VINCENZO; et al. Activity of human kallikrein-related peptidase 6 (KLK6) on substrates containing sequences of basic amino acids. Is it a processing protease?. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1865, n. 5, p. 558-564, . (12/50191-4)
DE SOUZA, EDUARDO SERGIO; KATAGIRI, ALBERTO H.; JULIANO, LUIZ; JULIANO, MARIA APARECIDA; PIMENTA, DANIEL CARVALHO; ITO, AMANDO SIUITI. Fret Studies of Conformational Changes in Heparin-Binding Peptides. Journal of Fluorescence, v. 24, n. 3, p. 885-894, . (12/50191-4)
OLIVEIRA, LILIAN C. G.; OKAMOTO, DEBORA N.; OLIVEIRA, JULIANA R.; KONDO, MARCIA Y.; GOUVEA, IURI E.; BITEAU, NICOLAS; BALTZ, THEO; MURAKAMI, MARIO T.; JULIANO, LUIZ; JULIANO, MARIA A.. Analysis of peptidase activities of a cathepsin B-like (TcoCBc1) from Trypanosoma congolense. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1844, n. 7, p. 1260-1267, . (12/50191-4)
ALENCAR BEZERRA, TALIANA KENIA; JOCELINO GOMES DE LACERDA, JOSE THALLES; SALU, BRUNO RAMOS; VILELA OLIVA, MARIA LUIZA; JULIANO, MARIA APARECIDA; PACHECO, MARIA TERESA BERTOLDO; MADRUGA, MARTA SUELY. Identification of Angiotensin I-Converting Enzyme-Inhibitory and Anticoagulant Peptides from Enzymatic Hydrolysates of Chicken Combs and Wattles. JOURNAL OF MEDICINAL FOOD, v. 22, n. 12, . (18/13588-0, 12/50191-4)
TELES, CATHERINE M.; ANTUNES, VICTOR U.; CARDOSO, RAQUEL S.; CANDIDO, TUANY Z.; LIMA, CARMEN S. P.; RUIZ, ANA LUCIA T. G.; JULIANO, MARIA A.; FAVARO, DENIZE C.; ABBEHAUSEN, CAMILLA. Functionalization of new anticancer Pt(II) complex with transferrin receptor binding peptide. Inorganica Chimica Acta, v. 511, . (19/16904-2, 16/07729-4, 12/50191-4)
ASSIS, DIEGO M.; JULIANO, LUIZ; PASCHOALIN, THAYSA; KOUYOUMDJIAN, MARIA; CALIXTO, JOAO B.; SANTOS, ROBSON A. S.; PERTINHEZ, THELMA A.; GAUTHIER, FRANCIS; MOREAU, THIERRY; BLABER, MICHAEL; et al. Pharmacological Activities and Hydrolysis by Peptidases of [Phospho-Ser(6)]-Bradykinin (pS(6)-BK). Biochemical Pharmacology, v. 97, n. 2, p. 203-214, . (12/50191-4)
HAMIN NETO, YOUSSEF A. A.; DE OLIVEIRA, LILIAN C. G.; DE OLIVEIRA, ARTHUR H. C.; ROSA, JOSE C.; JULIANO, MARIA A.; JULIANO, LUIZ; RODRIGUES, ANDRE; CABRAL, HAMILTON. Determination of Specificity and Biochemical Characteristics of Neutral Protease Isolated from Myceliophthora thermophila. PROTEIN AND PEPTIDE LETTERS, v. 22, n. 11, p. 972-982, . (12/18278-2, 11/06986-0, 12/50191-4, 12/24703-8)
OLIVEIRA, JOCELIA P. C.; FREITAS, RENATO F.; DE MELO, LEANDRO SILVA; BARROS, THALITA G.; SANTOS, JORGE A. N.; JULIANO, MARIA A.; PINHEIRO, SERGIO; BLABER, MICHAEL; JULIANO, LUIZ; MURI, ESTELA M. F.; et al. Isomannide-Based Peptidomimetics as Inhibitors for Human Tissue Kallikreins 5 and 7. ACS Medicinal Chemistry Letters, v. 5, n. 2, p. 128-132, . (12/50191-4, 11/51297-8)
PEREIRA, FELIPE V.; FERREIRA-GUIMARAES, CARLA A.; PASCHOALIN, THAYSA; SCUTTI, JORGE A. B.; MELO, FILIPE M.; SILVA, LUIS S.; MELO, AMANDA C. L.; SILVA, PRISCILA; TIAGO, MANOELA; MATSUO, ALISSON L.; et al. A Natural Bacterial-Derived Product, the Metalloprotease Arazyme, Inhibits Metastatic Murine Melanoma by Inducing MMP-8 Cross-Reactive Antibodies. PLoS One, v. 9, n. 4, . (10/51423-0, 12/50191-4)
DE OLIVEIRA, TALITA MENDES; JOCELINO GOMES DE LACERDA, JOSE THALLES; FIGUEIREDO LEITE, GIUSEPPE GIANINI; DIAS, MERIELLEN; MENDES, MARIA ANITA; KASSAB, PAULO; SALES E SILV, CLISLEYD GLAUCIELLY; JULIANO, MARIA APARECIDA; FORONES, NORA MANOUKIAN. Label-free peptide quantification coupled with in silico mapping of proteases for identification of potential serum biomarkers in gastric adenocarcinoma patients. CLINICAL BIOCHEMISTRY, v. 79, p. 61-69, . (18/13588-0, 12/50191-4)
BEZERRA, TALIANA; ESTEVEZ, MARIO; LACERDA, JOSE THALLES; DIAS, MERIELLEN; JULIANO, MARIA; MENDES, MARIA ANITA; MORGANO, MARCELO; PACHECO, MARIA TERESA; MADRUGA, MARTA. Chicken Combs and Wattles as Sources of Bioactive Peptides: Optimization of Hydrolysis, Identification by LC-ESI-MS2 and Bioactivity Assessment. Molecules, v. 25, n. 7, . (18/13588-0, 12/50191-4)
RAMOS, PATRICIA L.; KONDO, MARCIA Y.; SANTOS, SAARA M. B.; DE VASCONCELLOS, SUZAN P.; ROCHA, RAFAEL C. S.; DA CRUZ, JOAO B.; EUGENIO, PATRICIA F. M.; CABRAL, HAMILTON; JULIANO, MARIA A.; JULIANO, LUIZ; et al. A Tropical Composting Operation Unit at SAo Paulo Zoo as a Source of Bacterial Proteolytic Enzymes. Applied Biochemistry and Biotechnology, v. 187, n. 1, p. 282-297, . (14/07037-0, 12/50191-4, 13/12106-8, 11/06548-2)
INDARTE, MARTIN; LAZZA, CRISTIAN M.; ASSIS, DIEGO; CAFFINI, NESTOR O.; JULIANO, MARIA A.; AVILES, FRANCESC X.; DAURA, XAVIER; LOPEZ, LAURA M. I.; TREJO, SEBASTIAN A.. A Bowman-Birk protease inhibitor purified, cloned, sequenced and characterized from the seeds of Maclura pomifera (Raf.) Schneid. PLANTA, v. 245, n. 2, p. 343-353, . (12/50191-4)
SEVERINO, BEATRICE; FIORINO, FERDINANDO; CORVINO, ANGELA; CALIENDO, GIUSEPPE; SANTAGADA, VINCENZO; ASSIS, DIEGO MAGNO; OLIVEIRA, JULIANA R.; JULIANO, LUIZ; MANGANELLI, SERENA; BENFENATI, EMILIO; et al. Synthesis, biological evaluation, and docking studies of PAR2-AP-derived pseudopeptides as inhibitors of kallikrein 5 and 6. Biological Chemistry, v. 396, n. 1, p. 45-52, . (12/50191-4)
KONDO, MARCIA Y.; GOUVEA, IURI E.; OKAMOTO, DEBORA N.; SANTOS, JORGE A. N.; SOUCCAR, CADEN; ODA, KOHEI; JULIANO, LUIZ; JULIANO, MARIA A.. Analysis of catalytic properties of tripeptidyl peptidase I (TTP-I), a serine carboxyl lysosomal protease, and its detection in tissue extracts using selective FRET peptide substrate. Peptides, v. 76, p. 80-86, . (13/12106-8, 12/50191-4)
RIBEIRO GOMES MAIA, ANA CAROLINA; PORCINO, GABRIANE NASCIMENTO; FARIA-PINTO, PRISCILA; MENDES, TULIO VIEIRA; RIBEIRO ANTINARELLI, LUCIANA MARIA; COIMBRA, ELAINE SOARES; REIS, ALEXANDRE BARBOSA; JULIANO, LUIZ; JULIANO, MARIA APARECIDA; MARQUES, MARCOS JOSE; et al. Leishmania infantum nucleoside triphosphate diphosphohydrolase 1 (NTPDase 1) B-domain: Antibody antiproliferative effect on the promastigotes and IgG subclass responses in canine visceral leishmaniasis. Veterinary Parasitology, v. 271, p. 38-44, . (12/50191-4)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
Filed patent(s) as a result of this research project

MÉTODO DE IDENTIFICAÇÃO DE COMPOSTOS ANTIVIRAIS, COMPOSTOS ANTIVIRAIS, MÉTODO DE AVALIAÇÃO DA FUNCIONALIDADE DOS COMPOSTOS ANTIVIRAIS, USO DOS COMPOSTOS ANTIVIRAIS E COMPOSIÇÃO FARMACÊUTICA ANTIVIRAL BR1020150065612 - Universidade de São Paulo (USP) ; Universidade Federal de São Paulo (UNIFESP) . Antonia Tavares do Amaral; Erika Piccirillo; Maria Aparecida Juliano; Marcia Yuri Kondo - March 2015, 24