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Isolation and characterization of Psalmopeotoxin I and II: two novel antimalarial peptides from the venom of the tarantula Psalmopoeus cambridgei
Author(s) -
Choi Soo-Jin,
Parent Romain,
Guillaume Carole,
Deregnaucourt Christiane,
Delarbre Christiane,
Ojcius David M,
Montagne Jean-Jacques,
Célérier Marie-Louise,
Phelipot Aude,
Amiche Mohamed,
Molgo Jordi,
Camadro Jean-Michel,
Guette Catherine
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.07.019
Subject(s) - peptide , plasmodium falciparum , venom , biology , biochemistry , peptide sequence , in vitro , signal peptide , amino acid , immunology , gene , malaria
Two novel peptides that inhibit the intra‐erythrocyte stage of Plasmodium falciparum in vitro were identified in the venom of the Trinidad chevron tarantula, Psalmopoeus cambridgei . Psalmopeotoxin I (PcFK1) is a 33‐residue peptide and Psalmopeotoxin II (PcFK2) has 28‐amino acid residues; both have three disulfide bridges and belong to the Inhibitor Cystine Knot superfamily. The cDNAs encoding both peptides were cloned, and nucleotide sequence analysis showed that the peptides are synthesized with typical signal peptides and pro‐sequences that are cleaved at a basic doublet before secretion of the mature peptides. The IC 5O of PcFK1 for inhibiting P. falciparum growth was 1.59 ± 1.15 μM and that of PcFK2 was 1.15 ± 0.95 μM. PcFK1 was adsorbed strongly to uninfected erythrocytes, but PcFK2 was not. Neither peptide has significant hemolytic activity at 10 μM. Electrophysiological recordings in isolated frog and mouse neuromuscular preparations revealed that the peptides (at up to 9.3 μM) do not affect neuromuscular transmission or quantal transmitter release. PcFK1 and PcFK2 do not affect the growth or viability of human epithelial cells, nor do they have any antifungal or antibacterial activity at 20 μM. Thus, PcFK1 and PcFK2 seem to interact specifically with infected erythrocytes. They could therefore be promising tools for antimalaria research and be the basis for the rational development of antimalarial drugs.