Cyclic peptide somatostatin analogs
AssigneeDiatech, Inc.
InventorsRichard T. Dean, William McBride, John Lister-James
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Abstract
This invention relates to therapeutic reagents and peptides, including radiotherapeutic reagents and peptides, and radiodiagnostic reagents and peptides. Specifically, the invention relates to cyclic peptide derivatives and analogs of somatostatin, and embodiments of such peptides radiolabeled with a radioisotope, as well as methods for using such peptides for radiodiagnostic and radiotherapeutic purposes.
Claims23
A composition comprising a somatostatin receptor-binding peptide having a formula:
- cyclo(A.sup.4 -B.sup.1 B.sup.2 B.sup.3 B.sup.4 -C.sup.4)
- wherein
- B.sup.1 is D- or L-Phe or D- or L-Tyr or D- or L-Nal or Ain or a substituted derivative thereof;
- B.sup.2 is D- or L-Trp or a substituted derivative thereof;
- B.sup.3 is D- or L-Lys or Hly, Achxa, Amf, Aec, Apc, Aes, Aps or a substituted derivative thereof;
- B.sup.4 is Thr, Ser, Val, Phe, Ile, Abu, Nle, Leu, Nva or Aib;
- C.sup.4 is an .alpha.-amino acid having a sidechain covalently linked to an amino acid, an amino acid amide, a monosaccharide, an oligosaccharide comprising from 2 to about 10 saccharide residues, a polyoxanion, a thiol, an hydroxyl, a sulfonyl, a sulfonamide, a second peptide comprising from 2 to about 10 amino acid residues and having a carboxyl terminal carboxylic acid, or a second peptide comprising from 2 to about 10 amino acid residues and having a carboxyl terminal amide;
- and
- A.sup.4 is a lipophilic D-amino acid or a lipophilic L-(.alpha.-N-alkyl) amino acid or L-proline or a substituted derivative thereof;
- wherein the peptide is cyclized through a covalent linkage between an .alpha.-amino terminus of residue A.sup.4 and an .alpha.-carboxyl terminus of residue C.sup.4.
A composition comprising a somatostatin receptor-binding peptide having a formula:
- cyclo(A.sup.4 -B.sup.1 B.sup.2 B.sup.3 B.sup.4 -C.sup.4)
- wherein
- B.sup.1 is D- or L-Phe or D- or L-Tyr or D- or L-Nal or Ain or a substituted derivative thereof;
- B.sup.2 is D- or L-Trp or a substituted derivative thereof;
- B.sup.3 is D- or L-Lys or Hly, Achxa, Amf, Aec, Apc, Aes, Aps or a substituted derivative thereof;
- B.sup.4 is Thr, Ser, Val, Phe, Ile, Abu, Nle, Leu, Nva or Aib;
- A.sup.4 is a lipophilic D-amino acid or a lipophilic L-(.alpha.-N-alkyl) amino acid or
- L-proline or a substituted derivative thereof;
- C.sup.4 is an Lo:-amino acid having a sidechain
- --(CH.sub.2).sub.n SR.sup.1
- where n is an integer from 1-4 and R.sup.1 is H, lower alkyl, substituted alkyl, hydroxyalkyl, or alkoxyalkyl;
- wherein the peptide is cyclized through a covalent linkage between an .alpha.-amino terminus of residue A.sup.4 and an .alpha.-carboxyl terminus of residue C.sup.4.
A composition comprising at least two somatostatin receptor-binding peptides having a formula:
- (cyclo(A.sup.4 -B.sup.1 B.sup.2 B.sup.3 B.sup.4 -C.sup.4)).sub.m
- wherein
- B.sup.1 is D- or L-Phe or D- or L-Tyr or D- or L-Nal or Ain or a substituted derivative thereof;
- B.sup.2 is D- or L-Trp or a substituted thereof;
- B.sup.3 is D- or L-Lys or Hly, Achxa, Amf, Aec, Apc, Aes, Aps or a substituted thereof;
- B.sup.4 is Thr, Ser, Val, Phe, Ile, Abu, Nle, Leu, Nva or Aib;
- A.sup.4 is a lipophilic .alpha.-amino acid or a lipophilic L-((.alpha.-N-alkyl) amino acid or L-proline or a substituted derivative thereof;
- C.sup.4 is an .alpha.-amino acid having a sidechain --(CH.sub.2).sub.n SR.sup.2
- where n is an integer from 1-4 and R.sup.2 is selected from the group consisting of a bond covalently linking said peptides and a polyvalent linking moiety covalently linked to said peptides;
- m is an integer from 2 to 6;
- and wherein each of said peptides is cyclized through a covalent linkage between an .alpha.-amino terminus of residue A.sup.4 and an .alpha.-carboxyl terminus of residue C.sup.4.
Dependencies are inferred from the claim text.