A mutant streptokinase lacking the C-terminal 42 amino acids is less reactive with preexisting antibodies in patient sera

Streptokinase (SK) is an efficacious thrombolytic drug for the treatment of myocardial infarction. Because of its immunogenicity, patients receiving S K therapy develop high anti-SK antibody (Ab) titers, which might provoke se vere allergic reactions and neutralize SK activity. In this report we studi ed the reactivity of a synthetic 42-residue peptide resembling SKC-2 C-term inus with patient sera. SKC-2(373-414) peptide was recognized by 39 and 64% of patients, before and after SKC-2 therapy, respectively. An SKC-2 deleti on mutant (mut-C42), lacking the same 42 C-terminal residues, was construct ed and expressed in Escherichia coli. Recognition of mut-C42 by preexisting Abs from patient sera was 51 and 68% of reactivity to SKC-2, as assessed b y direct binding and competition assays, respectively. For most of the pati ents, mut-C42-neutralizing activity titer (NAT) significantly decreased wit h respect to SKC-2-NAT. This study opens the possibility of producing a les s immunogenic variant of SK which could constitute a preferred alternative for thrombolytic therapy. (C) 1999 Academic Press.