PRODUCTION OF AN ATRIAL-NATRIURETIC-PEPTIDE VARIANT THAT IS SPECIFIC FOR TYPE-A RECEPTOR

Receptor-specific variants of atrial natriuretic peptide (ANP) were se lected from libraries of filamentous phage particles that displayed si ngle copies of random ANP mutants fused to gene III protein. These ANP variants were differentially selected by binding to immobilized natri uretic peptide receptor A (NPR-A) over competing receptor C (NPR-C) in solution. This method also selected ANP variants with improved secret ion expression in Escherichia coli. Several of the identified mutation s were combined to produce an efficiently expressed ANP analog that wa s as potent as wild-type ANP in stimulating NPR-A guanylyl cyclase act ivity but resistant to inactivation mediated by NPR-C. Such NPR-A-sele ctive analogs should be useful for correlating the various activities of ANP to the relevant receptor and may also be more potent therapeuti cs in the targeting of NPR-A.