Development of inhibitors of Plasmodium falciparum apical membrane antigen 1 based on fragment screening

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Apical membrane antigen 1 (AMA1) is an essential component of the moving junction complex used by Plasmodium falciparum to invade human red blood cells. AMA1 has a conserved hydrophobic cleft that is the site of key interactions with the rhoptry neck protein complex. Our goal is to develop small molecule inhibitors of AMA1 with broad strain specificity, which we are pursuing using a fragment-based approach. In our screening campaign, we identified fragments that bind to the hydrophobic cleft with a hit rate of 5 . The high hit rate observed strongly suggests that a druggable pocket is present within the cleft.
Original languageEnglish
Pages (from-to)1530 - 1536
Number of pages7
JournalAustralian Journal of Chemistry
Volume66
Issue number12
DOIs
Publication statusPublished - 2013

Cite this

@article{8237f979a97242aba1b5f966ac4f60e4,
title = "Development of inhibitors of Plasmodium falciparum apical membrane antigen 1 based on fragment screening",
abstract = "Apical membrane antigen 1 (AMA1) is an essential component of the moving junction complex used by Plasmodium falciparum to invade human red blood cells. AMA1 has a conserved hydrophobic cleft that is the site of key interactions with the rhoptry neck protein complex. Our goal is to develop small molecule inhibitors of AMA1 with broad strain specificity, which we are pursuing using a fragment-based approach. In our screening campaign, we identified fragments that bind to the hydrophobic cleft with a hit rate of 5 . The high hit rate observed strongly suggests that a druggable pocket is present within the cleft.",
author = "Lim, {San Sui} and Cael Debono and MacRaild, {Christopher Andrew} and Chandrashekaran, {Indu Rajmohan} and Olan Dolezal and Anders, {Robin F} and Simpson, {Jamie Scott} and Martin Scanlon and Shane Devine and Scammells, {Peter John} and Norton, {Raymond Stanley}",
year = "2013",
doi = "10.1071/CH13266",
language = "English",
volume = "66",
pages = "1530 -- 1536",
journal = "Australian Journal of Chemistry",
issn = "0004-9425",
publisher = "CSIRO Publishing",
number = "12",

}

Development of inhibitors of Plasmodium falciparum apical membrane antigen 1 based on fragment screening. / Lim, San Sui; Debono, Cael; MacRaild, Christopher Andrew; Chandrashekaran, Indu Rajmohan; Dolezal, Olan; Anders, Robin F; Simpson, Jamie Scott; Scanlon, Martin; Devine, Shane; Scammells, Peter John; Norton, Raymond Stanley.

In: Australian Journal of Chemistry, Vol. 66, No. 12, 2013, p. 1530 - 1536.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Development of inhibitors of Plasmodium falciparum apical membrane antigen 1 based on fragment screening

AU - Lim, San Sui

AU - Debono, Cael

AU - MacRaild, Christopher Andrew

AU - Chandrashekaran, Indu Rajmohan

AU - Dolezal, Olan

AU - Anders, Robin F

AU - Simpson, Jamie Scott

AU - Scanlon, Martin

AU - Devine, Shane

AU - Scammells, Peter John

AU - Norton, Raymond Stanley

PY - 2013

Y1 - 2013

N2 - Apical membrane antigen 1 (AMA1) is an essential component of the moving junction complex used by Plasmodium falciparum to invade human red blood cells. AMA1 has a conserved hydrophobic cleft that is the site of key interactions with the rhoptry neck protein complex. Our goal is to develop small molecule inhibitors of AMA1 with broad strain specificity, which we are pursuing using a fragment-based approach. In our screening campaign, we identified fragments that bind to the hydrophobic cleft with a hit rate of 5 . The high hit rate observed strongly suggests that a druggable pocket is present within the cleft.

AB - Apical membrane antigen 1 (AMA1) is an essential component of the moving junction complex used by Plasmodium falciparum to invade human red blood cells. AMA1 has a conserved hydrophobic cleft that is the site of key interactions with the rhoptry neck protein complex. Our goal is to develop small molecule inhibitors of AMA1 with broad strain specificity, which we are pursuing using a fragment-based approach. In our screening campaign, we identified fragments that bind to the hydrophobic cleft with a hit rate of 5 . The high hit rate observed strongly suggests that a druggable pocket is present within the cleft.

UR - http://www.publish.csiro.au.ezproxy.lib.monash.edu.au/?paper=CH13266

U2 - 10.1071/CH13266

DO - 10.1071/CH13266

M3 - Article

VL - 66

SP - 1530

EP - 1536

JO - Australian Journal of Chemistry

JF - Australian Journal of Chemistry

SN - 0004-9425

IS - 12

ER -