Claims
- 1. A polypeptide compound useful as a natriuretic, diuretic, and/or vasodilator in mammals, said polypeptide compound having the formula: ##STR33## wherein X is hydrogen, amido, acetyl, or an oligopeptide of up to 125 amino acid residues from the naturally occurring N-terminal Atrial Peptide Sequence, including the N-acetyl derivatives thereof;
- Y is hydroxyl, amido, Asn-OH, Asn-Ser-OH, Asn-Ser-Phe-OH, Asn-Ser-Phe-Arg-OH, Asn-Ser-Phe-Arg-Tyr-OH, or the C-terminal amide derivatives thereof; or an oligopeptide extension of up to 20 amino acid residues from the C-terminus of any of the foregoing, including the C-terminal amide derivatives thereof;
- each of AA.sub.6, AA.sub.7, AA.sub.13, and AA.sub.17 is independently selected from the group consisting of Gly and Ala; AA.sub.9 is selected from Ile, Met, and Val; and AA.sub.12 is selected from Ile and Val,
- wherein 0, 1 or 2 are by the D-isomer thereof, and including such compound containing a disulfide bridge joining the cysteine residues and the pharmacologically acceptable salts thereof,
- with the proviso that when AA.sub.6, AA.sub.7, AA.sub.13, and AA.sub.17 are Gly, AA.sub.9 is Ile or Met, AA.sub.12 is Ile, and Y is AsnOH, Asn-Ser-OH, Asn-Ser-Phe-OH, Asn-Ser-Phe-Arg-OH or Asn-Ser-Phe-Arg-Try-OH or the C-terminal amide derivatives thereof, and X is H or contains Arg as its C-terminal amino acid, at least one of the residues must be replaced by the D-isomer thereof.
- 2. A polypeptide compound in accordance with claim 1 wherein the compound is selected from the group consisting of:
- H-Arg-Ser-Ser-Cye-Phe-Gly-Gly-Arg-(D-Met)-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-(D-Cys)-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-(D-Phe)-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-(D-Ala)-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-(D-Ala)-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-(D-Arg)-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-(D-Val)-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-(D-Arg)-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-(D-Val)-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-(D-Ala)-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-(D-Ala)-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-(D-Gln)-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-(D-Ser)-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-(D-Ala)-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-(D-Leu)-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH
- including such compound containing a disulfide bridge joining the cysteine residues, and the pharmacologically acceptable salts thereof.
- 3. A pharmaceutical composition comprising a polypeptide compound in accordance with any of claims 1 or 2 in a therapeutically effective amount, together with a physiologically suitable carrier.
- 4. A method for inducing natriuresis, diuresis, vasodilatation, inhibiting renin secretion or modulating angiotensin-induced aldosterone release in a mammalian host, which comprises administering to said host a pharmaceutically effective amount of the compound or composition of any of claims 1, 2 or 3.
RELATED APPLICATION DATA
This application is a continuation-in-part of commonly owned and co-pending U.S. application Ser. No 602,117, filed Apr. 19, 1984, now U.S. Pat. Nos. 4,618,600, and No. 616,488, filed June 1, 1984.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US85/00658 |
4/16/1985 |
|
|
5/8/1985 |
5/8/1985 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO85/04870 |
11/7/1985 |
|
|
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
4496544 |
Needleman |
Jan 1985 |
|
4557864 |
Needleman |
Dec 1985 |
|
4607023 |
Thibault et al. |
Aug 1986 |
|
Non-Patent Literature Citations (9)
Entry |
Biochem. and Biophys. Res. Commun. 859-865, vol. 117, (1983). |
Science, vol. 223 (1984) 67-69. |
FEBS 1268, vol. 167, No. 2 (1984) 352-357. |
Biochem. and Biophys. Res. Commun. 524-529, vol. 119, No. 2 (1984). |
Biochem. and Biophys. Res. Commun. 131-139, vol. 118 (1984). |
The Journal of Histochemistry and Cytochemistry, vol. 26, No. 12 1094-1102 (1978). |
Life Sciences, vol. 28 pp. 89-94 (1980). |
Proceedings of the Society for Experimental Biology and Medicine 161, 508-511 (1979). |
Science, (1983) vol. 221 71-73. |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
602117 |
Apr 1984 |
|