RFamide-related peptides and methods thereof

Patent metadata

Field	Value
Publication number	US-9527889-B2
Application number	US-201414582553-A
Country	US
Kind code	B2
Filing date	Dec 24, 2014
Priority date	Apr 2, 2010
Publication date	Dec 27, 2016
Grant date	Dec 27, 2016

Abstract

Provided herein methods and compositions directed to RFRP-1 polypeptides for modulating cardiac contractile function, for preventing and/or treating cardiac disorders.

First claim

The invention claimed is:

1. An isolated peptide comprising the amino acid sequence of SEQ ID NO: 2 having
(i) one or more amino acid substitutions at amino acid positions 1-11 of SEQ ID NO: 2 and/or
(ii) an N-terminal truncation of no more than eight amino acids of SEQ ID NO: 2,
wherein said peptide comprises an amino acid at position 9 of SEQ ID NO: 2 that is P or a modified version thereof; an amino acid at position 10 of SEQ ID NO: 2 that is L or Q or a modified version thereof;
wherein the amino acid at position 5 of SEQ ID NO: 2, when present, is F or a modified version thereof; the amino acid at position 7 of SEQ ID NO: 2, when present, is N or a modified version thereof; wherein the amino acid at position 11 is not R;
wherein said peptide comprises a modified amino acid at one or more amino acid positions 1-11 of SEQ ID NO: 2, said modified amino acid being a D-amino acid, or a chemical compound used as an alternative to an amino acid in synthesis of peptidomimetic compounds, an amino acid derivative, a synthetic amino acid, or a non-native amino acid,
and said peptide modulates cardiac function in a vertebrate; or a salt, amide or ester thereof.

2. The peptide of claim 1 wherein the amino acid at position 3 of SEQ ID NO: 2, when present, is K, P, N, Bpa, or H or a modified version thereof;
the amino acid at position 4 of SEQ ID NO: 2, when present, is P or S or a modified version thereof;
the amino acid at position 6 of SEQ ID NO: 2, when present, is A or a modified version thereof;
the amino acid at position 8 of SEQ ID NO: 2, when present, is V, L, or A or a modified version thereof; and/or
the amino acid at position 11 of SEQ ID NO: 2 is A, or a modified version thereof.

3. The peptide of claim 1 , wherein the amino acid at position 11 of SEQ ID NO: 2 is A, V or L or a modified version thereof.

4. The peptide of claim 1 wherein the peptide comprises an N-terminal truncation of two amino acids.

5. The peptide of claim 1 , wherein the amino acid at position 3 of SEQ ID NO: 2, when present, is Bpa.

6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an isolated peptide according to claim 1 .

7. A method of screening for a compound that modulates cardiac function in a vertebrate, said method comprising:
contacting a group of one or more myocytes with an isolated peptide of claim 1 , and measuring an effect indicative of cardiac function in said group due to said contacting.

8. The peptide of claim 1 , comprising the amino acid sequence PLXF, PQXF, APLXF (SEQ ID NO: 5), APQXF (SEQ ID NO: 6), VPLXF (SEQ ID NO: 9), or VPQXF (SEQ ID NO: 10) at the C-terminus of the peptide, wherein X is any natural or modified amino acid other than L-arginine.

Assignees

• Univ Michigan Regents

Inventors

• Nichols Ruthann
• Westfall Margaret

Classifications

• C07K5/08

  Tripeptides · CPC title

• A61K38/08

  Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• G01N2500/10

  involving cells · CPC title

• G01N33/5061

  Muscle cells · CPC title

• C07K7/08 Primary

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title