The cDNA sequence encoding porcine brain natriuretic peptide and related genes
encoding canine and human peptides with natriuretic activity are disclosed. The
gene is shown to make accessible the DNAs encoding analogous natriuretic peptides
in other vertebrate species. The genes encoding these NPs can be used to effect
modifications of the sequence to produce alternate forms of the NPs and to provide
practical amounts of these proteins. The NPs of the invention can also be synthesized
chemically. The invention peptides have the formula:
R1-Cys-Phe-Gly-Arg- Arg/ - Leu/ -Asp-Arg-
Lys Met
&nb
Ile- Gly/ -Ser- Leu/ -Ser-Gly-Leu-Gly-Cys-R-2
Ser Ser
wherein R1 is selected from the group consisting of:
&nb
&nb
Ser
Asp/
Lys/ -Ser-Gly-;
Gly
Arg/ Asp/
His/ - Lys/ -Ser-Gly-;
Gln Gly
Arg/ Asp/
Met/ - His/ - Lys/ -Ser-Gly-;
Val Gln Gly
Arg/ Asp/
Thr/ - Met/ - His/ - Lys/ -Ser-Gly-;
Met Val Gln Gly
Arg/ Asp/
Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-;
Met Val Gln Gly
Arg/ Asp/
Pro-Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-;
Met Val Gln Gly
Arg/ Asp/
Ser-Pro-Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-;
Met Val Gln Gly
or a 10- to 109-amino acid sequence shown as the native upstream sequence for
porcine, canine or human BNP in FIG. 8, or a composite thereof;
- R2 is (OH), NH2, or NRR" wherein R
and R" are independently lower alkyl (1-4C) or is
Asn/
Lys
Asn/ -Val
Lys
Asn/ -Val-Leu
Lys
Asn/ -Val-Leu-Arg
Lys
Asn/ -Val-Leu-Arg- Arg/
Lys Lys
Asn/ -Val-Leu-Arg- Arg/ - Tyr/
Lys Lys His
or the amides (NH2 or NRR") thereof,
- with the proviso that if formula (1) is
R1-Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg-
Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R2
and R1 is Asp-Ser-Gly-, R2 cannot be Asn-Val-Leu-Arg-Arg-Tyr.
The peptides of the invention can be formulated into pharmaceutical compositions
and used to treat conditions associated with high extracellular fluid levels, especially
congestive heart failure.
