Trypanosoma brucei: killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Z-phe-ala-CHN2
Cysteine proteinases were tested for their suitability as targets for chemotherapy of sleeping sickness using the peptidyl inhibitor Z-Phe-Ala-diazomethyl ketone (Z-Phe-Ala-CHN2). In vitro, the inhibitory concentration of Z-Phe-Ala-CHN;2 required to reduce the growth rate by 50% was 400 times lower...
Gespeichert in:
| Hauptverfasser: | , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
1999
|
| In: |
Experimental parasitology
Year: 1999, Jahrgang: 91, Heft: 4, Pages: 327-333 |
| ISSN: | 1090-2449 |
| Online-Zugang: |
|
| Verfasserangaben: | S. Scory, C.R. Caffrey, Y.D. Stierhof, A. Ruppel, D. Steverding |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 175473698X | ||
| 003 | DE-627 | ||
| 005 | 20250730101754.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 210414s1999 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1006/expr.1998.4381 |2 doi | |
| 035 | |a (DE-627)175473698X | ||
| 035 | |a (DE-599)KXP175473698X | ||
| 035 | |a (OCoLC)1341404329 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Scory, Stefan |e VerfasserIn |0 (DE-588)1231392568 |0 (DE-627)1754739822 |4 aut | |
| 245 | 1 | 0 | |a Trypanosoma brucei |b killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Z-phe-ala-CHN2 |c S. Scory, C.R. Caffrey, Y.D. Stierhof, A. Ruppel, D. Steverding |
| 246 | 3 | 0 | |a Z-phe-ala-CHN 2 |
| 264 | 1 | |c 1999 | |
| 300 | |a 7 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Im Zusatz zum Titel ist die Zahl 2 tiefgestellt | ||
| 500 | |a Elektronische Reproduktion der Druck-Ausgabe | ||
| 500 | |a Gesehen am 14.04.2021 | ||
| 520 | |a Cysteine proteinases were tested for their suitability as targets for chemotherapy of sleeping sickness using the peptidyl inhibitor Z-Phe-Ala-diazomethyl ketone (Z-Phe-Ala-CHN2). In vitro, the inhibitory concentration of Z-Phe-Ala-CHN;2 required to reduce the growth rate by 50% was 400 times lower for culture-adapted bloodstream forms of Trypanosoma brucei than for a mouse myeloma cell line. At an inhibitor concentration of 10;M the parasites were lysed within 48 h of incubation. Parasitemia of mice infected with T. brucei decreased to undetectable levels for 3 days following treatment with 250 mg/kg Z-Phe-Ala-CHN2 on days 3 to 6 after infection. Although parasitemia returned thereafter to control levels, infected mice treated with the inhibitor survived approximately twice as long as those treated with placebo. Z-Phe-Ala-CHN2 inhibited proteinolysis in lysosomes in vitro and almost completely blocked cysteine proteinase activity in vivo. The results demonstrate the importance of cysteine proteinase activity for survival of T. brucei and suggest that such activity is an appropriate target for antitrypanosomal chemotherapy. | ||
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Cysteine Proteinase Inhibitors | |
| 650 | 4 | |a Diazomethane | |
| 650 | 4 | |a Dose-Response Relationship, Drug | |
| 650 | 4 | |a Female | |
| 650 | 4 | |a Mice | |
| 650 | 4 | |a Mice, Inbred BALB C | |
| 650 | 4 | |a Multiple Myeloma | |
| 650 | 4 | |a Trypanosoma brucei brucei | |
| 650 | 4 | |a Trypanosomiasis, African | |
| 650 | 4 | |a Tumor Cells, Cultured | |
| 700 | 1 | |a Caffrey, Conor |e VerfasserIn |0 (DE-588)1231375051 |0 (DE-627)1754727921 |4 aut | |
| 700 | 1 | |a Stierhof, Y. D. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ruppel, Andreas |e VerfasserIn |0 (DE-588)111311472X |0 (DE-627)867066946 |0 (DE-576)165214546 |4 aut | |
| 700 | 1 | |a Steverding, Dietmar |e VerfasserIn |0 (DE-588)1084824175 |0 (DE-627)848748328 |0 (DE-576)16720761X |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Experimental parasitology |d Orlando, Fla. : Academic Press, 1951 |g 91(1999), 4, Seite 327-333 |h Online-Ressource |w (DE-627)266018157 |w (DE-600)1466937-7 |w (DE-576)104193700 |x 1090-2449 |7 nnas |a Trypanosoma brucei killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Z-phe-ala-CHN2 |
| 773 | 1 | 8 | |g volume:91 |g year:1999 |g number:4 |g pages:327-333 |g extent:7 |a Trypanosoma brucei killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Z-phe-ala-CHN2 |
| 951 | |a AR | ||
| 992 | |a 20210414 | ||
| 993 | |a Article | ||
| 994 | |a 1999 | ||
| 998 | |g 1084824175 |a Steverding, Dietmar |m 1084824175:Steverding, Dietmar |d 910000 |d 911700 |e 910000PS1084824175 |e 911700PS1084824175 |k 0/910000/ |k 1/910000/911700/ |p 5 | ||
| 998 | |g 111311472X |a Ruppel, Andreas |m 111311472X:Ruppel, Andreas |d 910000 |d 912800 |e 910000PR111311472X |e 912800PR111311472X |k 0/910000/ |k 1/910000/912800/ |p 4 | ||
| 998 | |g 1231392568 |a Scory, Stefan |m 1231392568:Scory, Stefan |d 910000 |d 911700 |e 910000PS1231392568 |e 911700PS1231392568 |k 0/910000/ |k 1/910000/911700/ |p 1 |x j | ||
| 999 | |a KXP-PPN175473698X |e 3909123139 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"type":{"media":"Online-Ressource","bibl":"article-journal"},"note":["Im Zusatz zum Titel ist die Zahl 2 tiefgestellt","Elektronische Reproduktion der Druck-Ausgabe","Gesehen am 14.04.2021"],"language":["eng"],"recId":"175473698X","person":[{"family":"Scory","given":"Stefan","roleDisplay":"VerfasserIn","display":"Scory, Stefan","role":"aut"},{"family":"Caffrey","given":"Conor","display":"Caffrey, Conor","roleDisplay":"VerfasserIn","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Stierhof, Y. D.","role":"aut","family":"Stierhof","given":"Y. D."},{"roleDisplay":"VerfasserIn","display":"Ruppel, Andreas","role":"aut","family":"Ruppel","given":"Andreas"},{"roleDisplay":"VerfasserIn","display":"Steverding, Dietmar","role":"aut","family":"Steverding","given":"Dietmar"}],"title":[{"title_sort":"Trypanosoma brucei","title":"Trypanosoma brucei","subtitle":"killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Z-phe-ala-CHN2"}],"physDesc":[{"extent":"7 S."}],"relHost":[{"title":[{"title_sort":"Experimental parasitology","title":"Experimental parasitology","subtitle":"EP"}],"pubHistory":["1.1951 -"],"titleAlt":[{"title":"EP"}],"part":{"extent":"7","volume":"91","text":"91(1999), 4, Seite 327-333","issue":"4","pages":"327-333","year":"1999"},"disp":"Trypanosoma brucei killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Z-phe-ala-CHN2Experimental parasitology","type":{"bibl":"periodical","media":"Online-Ressource"},"note":["Gesehen am 19.10.07"],"language":["eng"],"recId":"266018157","origin":[{"publisherPlace":"Orlando, Fla.","dateIssuedDisp":"1951-","publisher":"Academic Press","dateIssuedKey":"1951"}],"id":{"issn":["1090-2449"],"zdb":["1466937-7"],"eki":["266018157"]},"physDesc":[{"extent":"Online-Ressource"}]}],"name":{"displayForm":["S. Scory, C.R. Caffrey, Y.D. Stierhof, A. Ruppel, D. Steverding"]},"origin":[{"dateIssuedKey":"1999","dateIssuedDisp":"1999"}],"id":{"doi":["10.1006/expr.1998.4381"],"eki":["175473698X"]}} | ||
| SRT | |a SCORYSTEFATRYPANOSOM1999 | ||