Anti-malaria drug development targeting the M1 alanyl and M17 leucyl aminopeptidases

Karine Thivierge; Rency T. Mathew; Desire M. M. Nsangou; Fabio da Silva; Sophie Cotton; Tina S. Skinner-Adams; Katharine R. Trenholme; Christopher L. Brown; Colin M. Stack; Donald L. Gardiner; John P. Dalton

doi:10.3998/ark.5550190.0013.424

Anti-malaria drug development targeting the M1 alanyl and M17 leucyl aminopeptidases

Karine Thivierge, Rency T. Mathew, Desire M. M. Nsangou, Fabio da Silva, Sophie Cotton, Tina S. Skinner-Adams, Katharine R. Trenholme, Christopher L. Brown, Colin M. Stack, Donald L. Gardiner, John P. Dalton

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

4 Citations (Scopus)

Abstract

The M1 alanyl aminopeptidase and M17 leucyl aminopeptidase are critical to the growth and development of malaria parasites inside host erythrocytes. Potent aminopeptidase inhibitors kill malaria parasites in culture and are also active in vivo against murine malaria. Functional recombinant enzyme studies have been used to decipher the three-dimensional structures of both enzymes that together with new and specific inhibitors are facilitating structure-activity-relationship (SAR) and functional studies. Here we review the progress made in our knowledge of these two enzymes which is bringing them closer to being validated anti-malarial drug targets.

Original language	English
Pages (from-to)	330-346
Number of pages	17
Journal	ARKIVOC
Issue number	4
DOIs	https://doi.org/10.3998/ark.5550190.0013.424
Publication status	Published - 2012

Keywords

aminopeptidases
antimalarials
enzymes
hemoglobin
malaria
plasmodium

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3998/ark.5550190.0013.424

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title = "Anti-malaria drug development targeting the M1 alanyl and M17 leucyl aminopeptidases",

abstract = "The M1 alanyl aminopeptidase and M17 leucyl aminopeptidase are critical to the growth and development of malaria parasites inside host erythrocytes. Potent aminopeptidase inhibitors kill malaria parasites in culture and are also active in vivo against murine malaria. Functional recombinant enzyme studies have been used to decipher the three-dimensional structures of both enzymes that together with new and specific inhibitors are facilitating structure-activity-relationship (SAR) and functional studies. Here we review the progress made in our knowledge of these two enzymes which is bringing them closer to being validated anti-malarial drug targets.",

keywords = "aminopeptidases, antimalarials, enzymes, hemoglobin, malaria, plasmodium",

author = "Karine Thivierge and Mathew, {Rency T.} and Nsangou, {Desire M. M.} and {da Silva}, Fabio and Sophie Cotton and Skinner-Adams, {Tina S.} and Trenholme, {Katharine R.} and Brown, {Christopher L.} and Stack, {Colin M.} and Gardiner, {Donald L.} and Dalton, {John P.}",

year = "2012",

doi = "10.3998/ark.5550190.0013.424",

language = "English",

pages = "330--346",

journal = "ARKIVOC",

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TY - JOUR

T1 - Anti-malaria drug development targeting the M1 alanyl and M17 leucyl aminopeptidases

AU - Thivierge, Karine

AU - Mathew, Rency T.

AU - Nsangou, Desire M. M.

AU - da Silva, Fabio

AU - Cotton, Sophie

AU - Skinner-Adams, Tina S.

AU - Trenholme, Katharine R.

AU - Brown, Christopher L.

AU - Stack, Colin M.

AU - Gardiner, Donald L.

AU - Dalton, John P.

PY - 2012

Y1 - 2012

N2 - The M1 alanyl aminopeptidase and M17 leucyl aminopeptidase are critical to the growth and development of malaria parasites inside host erythrocytes. Potent aminopeptidase inhibitors kill malaria parasites in culture and are also active in vivo against murine malaria. Functional recombinant enzyme studies have been used to decipher the three-dimensional structures of both enzymes that together with new and specific inhibitors are facilitating structure-activity-relationship (SAR) and functional studies. Here we review the progress made in our knowledge of these two enzymes which is bringing them closer to being validated anti-malarial drug targets.

AB - The M1 alanyl aminopeptidase and M17 leucyl aminopeptidase are critical to the growth and development of malaria parasites inside host erythrocytes. Potent aminopeptidase inhibitors kill malaria parasites in culture and are also active in vivo against murine malaria. Functional recombinant enzyme studies have been used to decipher the three-dimensional structures of both enzymes that together with new and specific inhibitors are facilitating structure-activity-relationship (SAR) and functional studies. Here we review the progress made in our knowledge of these two enzymes which is bringing them closer to being validated anti-malarial drug targets.

KW - aminopeptidases

KW - antimalarials

KW - enzymes

KW - hemoglobin

KW - malaria

KW - plasmodium

UR - http://handle.uws.edu.au:8081/1959.7/521224

UR - http://www.arkat-usa.org/get-file/44538/

U2 - 10.3998/ark.5550190.0013.424

DO - 10.3998/ark.5550190.0013.424

M3 - Article

SN - 1551-7004

SP - 330

EP - 346

JO - ARKIVOC

JF - ARKIVOC

IS - 4

ER -

Anti-malaria drug development targeting the M1 alanyl and M17 leucyl aminopeptidases

Abstract

Keywords

UN SDGs

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