SYNTHETIC MACROPHAGE ACTIVATING PEPTIDES DERIVED FROM THE N-TERMINUS OF HUMAN MCF

Recently, we described the purification and N-terminal sequencing of a novel cytokine termed MCF (Monocyte Cytotoxicity Inducing Factor) (1,2). In order to study the interaction of this cytokine with monocytes, we synthesized a nona-peptide GAAVLEDSQ corresponding to the N-terminus of MCF: two truncated peptides, GAAVL and LEDSQ; and the substituted peptide, GAAVLENSQ. The authentic N-terminal peptide is biologically active in the nanomolar range, while substitution of asparagine for aspartic acid at position 7 diminishes biological activity. Biological activity was observed from the C-terminal fragment LEDSQ, but the N-terminal pentapeptide (GAAVL) was devoid of biological activity. Scatchard analysis revealed a single class of saturable high affinity sites. These studies indicate that the N-terminus of MCF is important in interacting with the binding site on monocytes and it may be possible to design synthetic activators and inhibitors of monocyte/macrophage cytotoxicity. (C) 1994 Academic Press, Inc.