SYNTHETIC PEPTIDES CORRESPONDING TO A REPETITIVE SEQUENCE OF MALARIALHISTIDINE-RICH PROTEIN BIND HEME AND INHIBIT HAEMOZOIN FORMATION IN-VITRO

Synthetic peptides containing a repetitive hexapeptide sequence (Ala-H is-His-Ala-Ala-Asp) of malarial histidine-rich protein II were evaluat ed for binding with haem in vitro. The pattern of haem binding suggest ed that each repeat unit of this sequence provides one binding site fo r haem. Chloroquine inhibited the haem-peptide complex formation with preferential formation of a haem-chloroquine complex. In vitro studies on haem polymerisation showed that none of the peptides could initiat e haemozoin formation. However, they could inhibit haemozoin formation promoted by a malarial parasite extract, possibly by competitively bi nding free haem. These results indicate this hexapeptide sequence repr esents the haem binding site of the malarial histidine-rich protein an d possibly the site of nucleation for haem polymerisation. (C) 1997 El sevier Science B.V.