10.1021/pr3005315.s001
Masayuki Morita
Masayuki
Morita
Hitomi Sanai
Hitomi
Sanai
Akiko Hiramoto
Akiko
Hiramoto
Akira Sato
Akira
Sato
Osamu Hiraoka
Osamu
Hiraoka
Takaya Sakura
Takaya
Sakura
Osamu Kaneko
Osamu
Kaneko
Araki Masuyama
Araki
Masuyama
Masatomo Nojima
Masatomo
Nojima
Yusuke Wataya
Yusuke
Wataya
Hye-Sook Kim
Hye-Sook
Kim
<i>Plasmodium falciparum</i> Endoplasmic
Reticulum-Resident Calcium Binding Protein Is a Possible Target of
Synthetic Antimalarial Endoperoxides, N‑89 and N‑251
American Chemical Society
2012
malaria parasites
antimalarial
PfERC
falciparum
CREC protein family
Synthetic Antimalarial Endoperoxides
endoperoxide structure
protein expression profiles
2012-12-07 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/_i_Plasmodium_falciparum_i_Endoplasmic_Reticulum_Resident_Calcium_Binding_Protein_Is_a_Possible_Target_of_Synthetic_Antimalarial_Endoperoxides_N_89_and_N_251/2462803
The endoperoxide artemisinin is a current first-line
antimalarial
and a critical component of the artemisinin-based combination therapies
(ACT) recommended by WHO for treatment of <i>Plasmodium falciparum</i>, the deadliest of malaria parasites. However, recent emergence of
the artemisinin-resistant <i>P. falciparum</i> urged us
to develop new antimalarial drugs. We have shown that synthetic endoperoxides
N-89 and its hydroxyl derivative N-251 had high antimalarial activities
both <i>in vivo</i> and <i>in vitro</i>. However,
the mechanisms including the cellular targets of the endoperoxide
antimalarials are not well understood. Thus, in this study, we employed
chemical proteomics to survey potential molecular targets of endoperoxides
by evaluating <i>P. falciparum</i> proteins capable to associate
with endoperoxide structure (N-346, a carboxyamino derivative of N-89).
We also analyzed the protein expression profiles of malaria parasites
treated with N-89 or N-251 to explore possible changes associated
with the drug action. From these experiments, we found that <i>P. falciparum</i> endoplasmic reticulum-resident calcium binding
protein (<i>Pf</i>ERC) had high affinity to the endoperoxide
structure (N-346) and was decreased by treatment with N-89 or N-251. <i>Pf</i>ERC is a member of CREC protein family, a potential disease
marker and also a potential target for therapeutic intervention. We
propose that the <i>Pf</i>ERC is a strong candidate of the
endoperoxide antimalarial’s target.