Isolation and characterization of Psalmopeotoxin I and II: two novel antimalarial peptides from the venom of the tarantula Psalmopoeus cambridgei.
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 microM and that of PcFK2 was 1.15+/-0.95 microM. PcFK1 was adsorbed strongly to uninfected erythrocytes, but PcFK2 was not. Neither peptide has significant hemolytic activity at 10 microM. Electrophysiological recordings in isolated frog and mouse neuromuscular preparations revealed that the peptides (at up to 9.3 microM) 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 microM. 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.
Laboratoire d'Ingénierie des Protéines et Contrôle Métabolique, Dept. de Biologie des Génomes, Institut Jacques Monod, UMR 7592, CNRS -- Universités Paris 6 and 7, 2 place Jussieu, 75251 Paris Cedex 05, France.
Soo-Jin
SJ
Choi
Romain
R
Parent
Carole
C
Guillaume
Christiane
C
Deregnaucourt
Christiane
C
Delarbre
David M
DM
Ojcius
Jean-Jacques
JJ
Montagne
Marie-Louise
ML
Célérier
Aude
A
Phelipot
Mohamed
M
Amiche
Jordi
J
Molgo
Jean-Michel
JM
Camadro
Catherine
C
Guette
D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001483:Base Sequence; D017124:Conserved Sequence; D008297:Male; D008969:Molecular Sequence Data; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011893:Rana esculenta; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013111:Spider Venoms / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D013112:Spiders
D000962:Antimalarials; D013111:Spider Venoms; C490709:psalmopeotoxin I, Psalmopoeus cambridgei; C490710:psalmopeotoxin II, Psalmopoeus cambridgei