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Specific fluorogenic substrates for neprilysin (neutral endopeptidase, EC 3.4.24.11) which are highly resistant to serine- and metalloproteases BJMBR
Medeiros,M.A.S.; França,M.S.F.; Boileau,G.; Juliano,L.; Carvalho,K.M..
Two intramolecularly quenched fluorogenic peptides containing o-aminobenzoyl (Abz) and ethylenediamine 2,4-dinitrophenyl (EDDnp) groups at amino- and carboxyl-terminal amino acid residues, Abz-<!-- $MVD$:face("Times") -->DArg-Arg-Leu-EDDnp (Abz-<!-- $MVD$:face("Times") -->DRRL-EDDnp) and Abz-<!-- $MVD$:face("Times") -->DArg-Arg-Phe-EDDnp (Abz-<!-- $MVD$:face("Times") -->DRRF-EDDnp), were selectively hydrolyzed by neutral endopeptidase (NEP, enkephalinase, neprilysin, EC 3.4.24.11) at the Arg-Leu and Arg-Phe bonds, respectively. The kinetic parameters for the NEP-catalyzed hydrolysis of Abz-<!-- $MVD$:face("Times") -->DRRL-EDDnp and Abz-<!-- $MVD$:face("Times") -->DRRF-EDDnp were Km = 2.8 µM, kcat = 5.3 min-1, kcat/Km = 2...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Neutral endopeptidase; Enkephalinase; Neprilysin; Fluorogenic substrates; Phosphoramidon.
Ano: 1997 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1997001000003
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A new brain metalloendopeptidase which degrades the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects BJMBR
Carvalho,K.M.; França,M.S.F.; Camarão,G.C.; Ruchon,A.F..
A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human brain using successive steps of chromatography on DEAE-Trisacryl, hydroxylapatite and Sephacryl S-200. The purified enzyme cleaved the Gly33-Leu34 bond of the 25-35 neurotoxic sequence of the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects. This enzyme activity was only inhibited by divalent cation chelators such as EDTA, EGTA and o-phenanthroline (1 mM) and was insensitive to phosphoramidon and captopril (1 µM concentration), specific inhibitors of neutral endopeptidase (EC 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. The high affinity of this human brain endopeptidase for ß-amyloid 1-40...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Brain metalloendopeptidase; Alzheimer ß-amyloid 1-40 peptide; Alzheimer's disease.
Ano: 1997 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1997001000002
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Partial sequence and toxic effects of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera BJMBR
Santana,A.N.C.; Leite,A.B.; França,M.S.F.; França,L.; Vale,O.C.; Cunha,R.B.; Ricart,C.A.O.; Sousa,M.V.; Carvalho,K.M..
A neurotoxic peptide, granulitoxin (GRX), was isolated from the sea anemone Bunodosoma granulifera. The N-terminal amino acid sequence of GRX is AKTGILDSDGPTVAGNSLSGT and its molecular mass is 4958 Da by electrospray mass spectrometry. This sequence presents a partial degree of homology with other toxins from sea anemones such as Bunodosoma caissarum, Anthopleura fuscoviridis and Anemonia sulcata. However, important differences were found: the first six amino acids of the sequence are different, Arg-14 was replaced by Ala and no cysteine residues were present in the partial sequence, while two cysteine residues were present in the first 21 amino acids of other toxins described above. Purified GRX injected ip (800 µg/kg) into mice produced severe neurotoxic...
Tipo: Info:eu-repo/semantics/other Palavras-chave: Bunodosoma granulifera; Sea anemones; Toxic peptides.
Ano: 1998 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1998001000015
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A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide BJMBR
Carvalho,K.M.; Nava,R.A.; França,M.S.F.; Medeiros,M.A.S.; Camarão,G.C.; Juliano,L..
A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 µM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. With Mr 85 kDa, the enzyme exhibits optimal...
Tipo: Info:eu-repo/semantics/other Palavras-chave: Liver metalloendopeptidase; Bradykinin; Atrial natriuretic peptide.
Ano: 1999 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1999000100007
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Behavioral and electroencephalographic analysis of seizures induced by intrahippocampal injection of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera BJMBR
Santana,A.N.C.; Trindade-Filho,E.M.; Cunha,R.B.; Sousa,M.V.; Cavalheiro,E.A.; Carvalho,K.M..
In this study, the behavioral and electroencephalographic (EEG) analysis of seizures induced by the intrahippocampal injection in rats of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera, was determined. The first alterations occurred during microinjection of granulitoxin (8 µg) into the dorsal hippocampus and consisted of seizure activity that began in the hippocampus and spread rapidly to the occipital cortex. This activity lasted 20-30 s, and during this period the rats presented immobility. During the first 40-50 min after its administration, three to four other similar short EEG seizure periods occurred and the rats presented the following behavioral alterations: akinesia, facial automatisms, head tremor, salivation,...
Tipo: Info:eu-repo/semantics/other Palavras-chave: Bunodosoma granulifera; Granulitoxin; Sea anemones; Toxic peptides; Seizure; Electroencephalographic assay.
Ano: 2001 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2001000600016
Registros recuperados: 5
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