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• W1519390411 abstract "Peptidases of Leishmania are acknowledged virulence factors. It is hypothesised that peptidases are crucial for the survival of Leishmania in its hosts and that many could be potential targets for new antileishmanial drugs. As such, the investigation of peptidase activity in live Leishmania promastigotes was proposed as a valuable approach by which to increase knowledge on particular peptidases. In order to complete this investigation, it was decided to use short peptidyl fluorogenic substrates, which only fluoresce once the bond linking the peptide to the fluorescent moiety is cleaved. These allow detection of peptidase activity by quantifying the release of the fluorescent moiety.Detection of peptidase activity in live Leishmania using the fluorogenic substrate Bz-R-AMC proved fruitful, enabling study of the activity of the serine peptidase oligopeptidase B (OPB) in live L. major promastigotes. OPB is a member of the Family S9 peptidases, the prolyl-oligopeptidases, which are taxonomically restricted to plants, bacteria and trypanosomatid flagellates. In African and American trypanosomes, OPB has been shown to have important roles: OPB is a virulence factor in Trypanosoma cruzi, mediating entry into host cells, and OPB is released into the serum by African trypanosomes, where it cleaves host blood factors.In this study, the inhibition profile of L. major OPB has been determined and OPB has been localised to the cytosol, the site of hydrolysis of Bz-R-AMC. Immunoprecipitation of OPB confirmed that OPB was the sole peptidase responsible for the hydrolysis of Bz-R-AMC and anti-OPB antibodies were found to inhibit the hydrolysis of Bz-R-AMC. Inhibitors of OPB could also kill Leishmania promastigotes, suggesting OPB could be a valuable drug target.However, genetic manipulation of OPB was successful, with mutants over-expressing OPB and opb null mutants produced. OPB is thus not essential for the growth of promastigote L. major, though the opb null mutants did have a defect in metacyclogenesis, in survival in macrophages and a reduced ability to induce lesions on the footpads of mice. A role in amastigote differentiation or survival in macrophages was also suggested. OPB is thus likely to be a virulence factor, though not essential, and thus not suitable as a primary drug target. A number of avenues require further investigation, including the need for re-expression of OPB in the opb null mutants to confirm that lack of OPB is indeed responsible for the phenotypic deficiencies of the null mutants. Other important areas requiring attention are investigation of the role of OPB in amastigote differentiation or survival, investigation of the reported release of OPB by promastigotes, and identification of the physiological substrate of OPB." @default.
• W1519390411 created "2016-06-24" @default.
• W1519390411 creator A5061648720 @default.
• W1519390411 date "2008-01-01" @default.
• W1519390411 modified "2023-09-24" @default.
• W1519390411 title "Studies on oligopeptidase B of Leishmania major" @default.
• W1519390411 cites W132994223 @default.
• W1519390411 cites W1479952727 @default.
• W1519390411 cites W1483346380 @default.
• W1519390411 cites W1488354887 @default.
• W1519390411 cites W1492030666 @default.
• W1519390411 cites W1501109059 @default.
• W1519390411 cites W1521464125 @default.
• W1519390411 cites W1543727318 @default.
• W1519390411 cites W1549139718 @default.
• W1519390411 cites W1549303292 @default.
• W1519390411 cites W1550745757 @default.
• W1519390411 cites W1557046906 @default.
• W1519390411 cites W1564221315 @default.
• W1519390411 cites W1573122700 @default.
• W1519390411 cites W1600346161 @default.
• W1519390411 cites W1605553518 @default.
• W1519390411 cites W1629416542 @default.
• W1519390411 cites W1651802458 @default.
• W1519390411 cites W1679104356 @default.
• W1519390411 cites W1764151989 @default.
• W1519390411 cites W1795427321 @default.
• W1519390411 cites W1797888712 @default.
• W1519390411 cites W1834582965 @default.
• W1519390411 cites W1866327908 @default.
• W1519390411 cites W1874018940 @default.
• W1519390411 cites W1910381980 @default.
• W1519390411 cites W1923641765 @default.
• W1519390411 cites W1946039171 @default.
• W1519390411 cites W1952065778 @default.
• W1519390411 cites W1958092593 @default.
• W1519390411 cites W1964395067 @default.
• W1519390411 cites W1965526161 @default.
• W1519390411 cites W1965801274 @default.
• W1519390411 cites W1966314292 @default.
• W1519390411 cites W1966362727 @default.
• W1519390411 cites W1968238739 @default.
• W1519390411 cites W1968540614 @default.
• W1519390411 cites W1968747252 @default.
• W1519390411 cites W1969687838 @default.
• W1519390411 cites W1970594670 @default.
• W1519390411 cites W1972489358 @default.
• W1519390411 cites W1973111776 @default.
• W1519390411 cites W1973339480 @default.
• W1519390411 cites W1973846011 @default.
• W1519390411 cites W1974924348 @default.
• W1519390411 cites W1975004033 @default.
• W1519390411 cites W1976174823 @default.
• W1519390411 cites W1976502466 @default.
• W1519390411 cites W1976519506 @default.
• W1519390411 cites W1976906421 @default.
• W1519390411 cites W1977082621 @default.
• W1519390411 cites W1977854038 @default.
• W1519390411 cites W1978166529 @default.
• W1519390411 cites W1980969503 @default.
• W1519390411 cites W1981242537 @default.
• W1519390411 cites W1983197520 @default.
• W1519390411 cites W1984243890 @default.
• W1519390411 cites W1984475667 @default.
• W1519390411 cites W1984483611 @default.
• W1519390411 cites W1984679061 @default.
• W1519390411 cites W1985469117 @default.
• W1519390411 cites W1985472780 @default.
• W1519390411 cites W1986522582 @default.
• W1519390411 cites W1987013095 @default.
• W1519390411 cites W1987546203 @default.
• W1519390411 cites W1988408881 @default.
• W1519390411 cites W1988564937 @default.
• W1519390411 cites W1989316445 @default.
• W1519390411 cites W1991297494 @default.
• W1519390411 cites W1991529476 @default.
• W1519390411 cites W1992033675 @default.
• W1519390411 cites W1992237103 @default.
• W1519390411 cites W1992402854 @default.
• W1519390411 cites W1993371274 @default.
• W1519390411 cites W1993548033 @default.
• W1519390411 cites W1993895246 @default.
• W1519390411 cites W1994276657 @default.
• W1519390411 cites W1995789505 @default.
• W1519390411 cites W1995892898 @default.
• W1519390411 cites W1996745525 @default.
• W1519390411 cites W1996791100 @default.
• W1519390411 cites W1997231586 @default.
• W1519390411 cites W1997545346 @default.
• W1519390411 cites W1997750876 @default.
• W1519390411 cites W1997886489 @default.
• W1519390411 cites W1998394184 @default.
• W1519390411 cites W1998531174 @default.
• W1519390411 cites W1999230968 @default.
• W1519390411 cites W1999357416 @default.
• W1519390411 cites W1999591398 @default.
• W1519390411 cites W2001819758 @default.
• W1519390411 cites W2001998466 @default.
• W1519390411 cites W2002994480 @default.
• W1519390411 cites W2003451501 @default.

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