RFamide-Related Peptides and Methods Thereof

1 . An isolated peptide comprising the amino acid sequence:

X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-F (SEQ ID NO: 13) wherein,

any one of amino acids X1 to X8 is present or absent, X9 and X11 are present, X10 is L or Q, and said peptide modulates cardiac function in a vertebrate; or a salt, amide or ester thereof.

2 . An isolated peptide comprising the amino acid sequence:

X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-F (SEQ ID NO: 13) wherein,

any one of amino acids X1 to X8 is present or absent, X9 and X11 are present, X10 is L or Q;

with the provisos that:

when said peptide consists of a pentapeptide, the amino acid sequence of said pentapeptide is not LPLRF (SEQ ID NO: 3); and when

said peptide consists of a dodecapeptide and X6, X7, X8, X9, X10, and X11 are each A, N, L, P, L, and R respectively, X4 is not S or P.

3 . The peptide of claim 2 wherein said peptide modulates cardiac function in a vertebrate.

4 . The peptide of claim 1 wherein X1 is an amino acid other than M, V, or S;

X5 is other than F, or V; X7 is other than N; X9 is other than P, and X11 is other than R; and wherein each of X1, X5, X7, X9, and X11 is independently selected from one another.

5 . The peptide of claim 1 wherein X11 is an amino acid other than R.

6 . The peptide of claim 4 wherein at least one of X1, X5, X7, X9, and X11 is A.

7 . The peptide of claim 1 , wherein X8 is present.

8 . The peptide of claim 7 , wherein X8 is A, V or L; and X9 is P or F.

9 . The peptide according to claim 1 wherein X2 is P, X4 is S; X6, X7, X8 and X9 are each respectively A, N, L, and P.

10 . The peptide of claim 1 , wherein at least one of X3 and X7 is an amino acid other than histidine.

11 . The peptide of claim 10 wherein X1 and X2 are absent.

12 . The peptide of claim 10 wherein X7 is A.

13 . (canceled)

14 . The peptide of claim 1 , wherein X3 is Bpa.

15 .- 20 . (canceled)

21 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an isolated peptide according to any one of claims 1 - 19 and 34 .

22 .- 24 . (canceled)

25 . A method of treating a cardiac disorder in a vertebrate, including a mammal, said method comprising administering to said vertebrate a therapeutically effective amount of the peptide of any one of claims 1 - 19 and 34 .

26 . A method of screening for an agent that modulates cardiac function in a vertebrate, said method comprising:

a) contacting a first group of one or more myocytes with an isolated peptide comprising a sequence selected from the group consisting of:

MPHSFANLPLRF (SEQ ID NO: 2); MPPSFANLPLRF (SEQ ID NO: 14); VPNSVANLPLRF (SEQ ID NO: 15); VPHSAANLPLRF (SEQ ID NO: 16);

MPPSAANLPLRF (SEQ ID NO: 17); SLKPAANLPLRF (SEQ ID NO: 18), LPLRF (SEQ ID NO: 3), PLRF, PQRF, FLRF, FQRF, APLRF (SEQ ID NO: 19), APQRF (SEQ ID NO: 20), AFLRF (SEQ ID NO: 21), AFQRF (SEQ ID NO: 22), VPLRF (SEQ ID NO: 23), VPQRF (SEQ ID NO: 24), VFLRF (SEQ ID NO: 25), and VFQRF (SEQ ID NO: 26), wherein F is amidated;

b) contacting the first group set forth in a), or a second group of one or more myocytes with a test agent; and measuring the effect subsequent to the contacting with the test agent; and

determining from the comparison of the measurement in step a) to that of step b) whether the test.

27 .- 31 . (canceled)

32 . A method of modulating PKC-mediated signal transduction in a cell or tissue of a vertebrate including a mammal, comprising contacting said cell or tissue with an isolated peptide comprising the amino acid sequence X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-F (SEQ ID NO: 13) wherein,

any one of amino acids X1 to X8 is present or absent, X9 and X11 are present, and X10 is L or Q; or a salt, amide or ester thereof.

33 .- 34 . (canceled)