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Titolo:
Identification of peptides inhibitory to recombinant cysteine proteinase, CPB, of Leishmania mexicana
Autore:
Alves, LC; St Hilaire, PM; Meldal, M; Sanderson, SJ; Mottram, JC; Coombs, GH; Juliano, L; Juliano, MA;
Indirizzi:
Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, BR-0404420 Sao Paulo, Brazil Univ Fed Sao Paulo Sao Paulo Brazil BR-0404420 0404420 Sao Paulo, Brazil Carlsberg Lab, Dept Chem, DK-2500 Copenhagen, Denmark Carlsberg Lab Copenhagen Denmark DK-2500 em, DK-2500 Copenhagen, Denmark Univ Glasgow, Inst Biomed & Life Sci, Div Infect & Immun, Glasgow G12 8QQ,Lanark, Scotland Univ Glasgow Glasgow Lanark Scotland G12 8QQ gow G12 8QQ,Lanark, Scotland Univ Glasgow, Anderson Coll, Wellcome Ctr Mol Parasitol, Glasgow G11 6NU, Lanark, Scotland Univ Glasgow Glasgow Lanark Scotland G11 6NU ow G11 6NU, Lanark, Scotland
Titolo Testata:
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
fascicolo: 1, volume: 114, anno: 2001,
pagine: 81 - 88
SICI:
0166-6851(20010425)114:1<81:IOPITR>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRYPANOSOMA-CRUZI; PROTEASE INHIBITORS; CATHEPSIN-B; PROCATHEPSIN-B; GENE ARRAY; PROPEPTIDE; PROMASTIGOTES; AMASTIGOTES; GP57/51; CHEMOTHERAPY;
Keywords:
thiol protease; cysteine proteinase; leishmania; inhibitors; cathepsin L; cruzain;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Juliano, MA Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Rua Tres Maio 100, BR-0404420 Sao Paulo, Brazil Univ Fed Sao Paulo Rua Tres Maio 100 Sao Paulo Brazil BR-0404420
Citazione:
L.C. Alves et al., "Identification of peptides inhibitory to recombinant cysteine proteinase, CPB, of Leishmania mexicana", MOL BIOCH P, 114(1), 2001, pp. 81-88

Abstract

We have identified peptides that are relatively resistant to hydrolysis bya recombinant cysteine proteinase, CPB2.8 Delta CTE, of Leishmania mexicana, and yet exhibit inhibition constant (K-i) values in the nanomolar range. Common to these peptides is a basic-hydrophobic-hydrophobic motif in the P-3-P-1 sites, which is also present in the pro-region of the enzyme. A nine-amino acid stretch, FAA (RYL) under bar NGA, which has good homology to the pro-region of mammalian cathepsin L was identified as the part of the pro-region most likely to interact with the active site of the parasite enzyme. This peptide is not hydrolyzed by CPB2.8 Delta CTE and inhibited it with a K-i of 4 muM. Extension of this sequence at both the N- and C-termini andthe introduction of ortho-aminobenzoic acid at the N-terminal site reducedthe K-i value to 30 nM. The best substrate for CPB2.8 Delta CTE was also well hydrolyzed by cathepsin L, however the best inhibitor of the parasite enzyme inhibit poorly cathepsin L, with K-i value two order of magnitude higher than against the parasite enzyme. These promising data provide insightsinto the peculiar specificity of the parasite enzyme and M ill aid the design of antiparasitic drugs directed against the leishmanial enzyme. (C) 2001 Elsevier Science B.V. All rights reserved.

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Documento generato il 15/07/20 alle ore 08:21:25