Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials

Tina S. Skinner-Adams; Colin M. Stack; Katharine R. Trenholme; Chris L. Brown; Jolanta Grembecka; Jonathan Lowther; Artur Mucha; Marcin Drag; Pawel Kafarski; Sheena McGowan; James C. Whisstock; Donald L. Gardiner; John P. Dalton

doi:10.1016/j.tibs.2009.08.004

Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials

Tina S. Skinner-Adams, Colin M. Stack, Katharine R. Trenholme, Chris L. Brown, Jolanta Grembecka, Jonathan Lowther, Artur Mucha, Marcin Drag, Pawel Kafarski, Sheena McGowan, James C. Whisstock, Donald L. Gardiner, John P. Dalton

School of Chemistry

Research output: Contribution to journal › Literature review › peer-review

Abstract / Description of output

The neutral aminopeptidases M1 alanyl aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) of the human malaria parasite Plasmodium falciparum are targets for the development of novel anti-malarial drugs. Although the functions of these enzymes remain unknown, they are believed to act in the terminal stages of haemoglobin degradation, generating amino acids essential for parasite growth and development. Inhibitors of both enzymes are lethal to P. falciparum in culture and kill the murine malaria P. chabaudi in vivo. Recent biochemical, structural and functional studies provide the substrate specificity and mechanistic binding data needed to guide the development of more potent antimalarial drugs. Together with biological studies, these data form the rationale for choosing PfM1AAP and PfM17LAP as targets for anti-malarial development.

Original language	English
Pages (from-to)	53-61
Number of pages	9
Journal	Trends in biochemical sciences
Volume	35
Issue number	1
DOIs	https://doi.org/10.1016/j.tibs.2009.08.004
Publication status	Published - Jan 2010

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Skinner-Adams, T. S., Stack, C. M., Trenholme, K. R., Brown, C. L., Grembecka, J., Lowther, J., Mucha, A., Drag, M., Kafarski, P., McGowan, S., Whisstock, J. C., Gardiner, D. L., & Dalton, J. P. (2010). Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials. Trends in biochemical sciences, 35(1), 53-61. https://doi.org/10.1016/j.tibs.2009.08.004

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title = "Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials",

abstract = "The neutral aminopeptidases M1 alanyl aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) of the human malaria parasite Plasmodium falciparum are targets for the development of novel anti-malarial drugs. Although the functions of these enzymes remain unknown, they are believed to act in the terminal stages of haemoglobin degradation, generating amino acids essential for parasite growth and development. Inhibitors of both enzymes are lethal to P. falciparum in culture and kill the murine malaria P. chabaudi in vivo. Recent biochemical, structural and functional studies provide the substrate specificity and mechanistic binding data needed to guide the development of more potent antimalarial drugs. Together with biological studies, these data form the rationale for choosing PfM1AAP and PfM17LAP as targets for anti-malarial development.",

author = "Skinner-Adams, {Tina S.} and Stack, {Colin M.} and Trenholme, {Katharine R.} and Brown, {Chris L.} and Jolanta Grembecka and Jonathan Lowther and Artur Mucha and Marcin Drag and Pawel Kafarski and Sheena McGowan and Whisstock, {James C.} and Gardiner, {Donald L.} and Dalton, {John P.}",

year = "2010",

month = jan,

doi = "10.1016/j.tibs.2009.08.004",

language = "English",

volume = "35",

pages = "53--61",

journal = "Trends in biochemical sciences",

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T1 - Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials

AU - Skinner-Adams, Tina S.

AU - Stack, Colin M.

AU - Trenholme, Katharine R.

AU - Brown, Chris L.

AU - Grembecka, Jolanta

AU - Lowther, Jonathan

AU - Mucha, Artur

AU - Drag, Marcin

AU - Kafarski, Pawel

AU - McGowan, Sheena

AU - Whisstock, James C.

AU - Gardiner, Donald L.

AU - Dalton, John P.

PY - 2010/1

Y1 - 2010/1

N2 - The neutral aminopeptidases M1 alanyl aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) of the human malaria parasite Plasmodium falciparum are targets for the development of novel anti-malarial drugs. Although the functions of these enzymes remain unknown, they are believed to act in the terminal stages of haemoglobin degradation, generating amino acids essential for parasite growth and development. Inhibitors of both enzymes are lethal to P. falciparum in culture and kill the murine malaria P. chabaudi in vivo. Recent biochemical, structural and functional studies provide the substrate specificity and mechanistic binding data needed to guide the development of more potent antimalarial drugs. Together with biological studies, these data form the rationale for choosing PfM1AAP and PfM17LAP as targets for anti-malarial development.

AB - The neutral aminopeptidases M1 alanyl aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) of the human malaria parasite Plasmodium falciparum are targets for the development of novel anti-malarial drugs. Although the functions of these enzymes remain unknown, they are believed to act in the terminal stages of haemoglobin degradation, generating amino acids essential for parasite growth and development. Inhibitors of both enzymes are lethal to P. falciparum in culture and kill the murine malaria P. chabaudi in vivo. Recent biochemical, structural and functional studies provide the substrate specificity and mechanistic binding data needed to guide the development of more potent antimalarial drugs. Together with biological studies, these data form the rationale for choosing PfM1AAP and PfM17LAP as targets for anti-malarial development.

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U2 - 10.1016/j.tibs.2009.08.004

DO - 10.1016/j.tibs.2009.08.004

M3 - Literature review

SN - 0968-0004

VL - 35

SP - 53

EP - 61

JO - Trends in biochemical sciences

JF - Trends in biochemical sciences

IS - 1

ER -

Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials

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