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US 4,505,853 AGranted
Enzyme-resistant immunomodulatory peptides
AssigneeOrtho Pharmaceutical Corporation
InventorsGideon Goldstein, George Heavner, Daniel Kroon, Tapan Audhya
Life of this patent
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Abstract
Peptides which have thymopoeitin-like or splenin-like activity combined with greatly increased resistance to degradation by enzymes. The peptides are useful for treatment of immunoregulatory disorders. Also provided are methods of treating immunoregulatory disorders and compositions used in these methods.
Claims28
A peptide having the formula:
- R--V--W--X--Y--Z--R.sup.1
- or a pharmaceutically acceptable acid- or base-addition salt thereof, wherein:
- R is H, NH.sub.2, acyl-NH, CH.sub.3 NH, or pyro-GLU-NH;
- ##STR5## W is PRO, dehydro PRO, or ##STR6## A individually is C.sub.2 -C.sub.6 loweralkyl;
- B individually is C.sub.1 -C.sub.3 loweralkyl;
- A and B taken together are --(CH.sub.2).sub.4 --or --(CH.sub.2).sub.5 --;
- X is D-ASP, ASP, D-GLU, or GLU;
- Y is GLY, VAL, LEU, nor-LEU, PHE, ILE, LYS, GLN, GLU, ALA, D-VAL, D-LEU, D- nor LEU, D-PHE, D-ILE, D-LYS, D-GLN, D-GLU, or D-ALA;
- Z is ##STR7## D is H or 1 or 2 substituents which increase or do not substantially decrease the acidity of the phenol proton;
- E is H or C.sub.1 -C.sub.3 loweralkyl;
- R.sup.1 is OH, NHR", ##STR8## and R" and R'" are individually H or lower alkyl;
- provided that V may be D- or L-isomer if R is other than H, and further provided that no more than one of V, X, and Y is a D amino acid.
9 more elements
A peptide having the formula:
- R--V--W--X--Y--Z--R.sup.1
- or a pharmaceutically acceptable acid- or base-addition salt thereof, wherein:
- R--V is acyl-ARG or acyl-D-ARG;
- W is PRO or AIB
- X is D-ASP, ASP, D-GLU, or GLU;
- Y is GLY, VAL, LEU, norLEU, PHE, ILE, LYS, GLN, GLU, ALA, D-VAL, D-LEU, D-norLEU, D-PHE, D-ILE, D-LYS, D-GLN, D-GLU, or D-ALA;
- Z is ##STR9## D is H or 1 or 2 substituents which increase or do not substantially decrease the acidity of the phenol proton;
- E is H or C.sub.1 -C.sub.3 loweralkyl;
- R.sup.1 is OH, NHR", ##STR10## and R" and R'" are individually H or lower alkyl;
- provided that no more than one of V, X, and Y is a D amino acid.
7 more elements
A peptide having the formula:
- R--V--W--X--Y--Z--R.sup.1
- or a pharmaceutically acceptable acid- or base-addition salt thereof, wherein:
- R--V is acyl-ARG;
- W is PRO or AIB;
- X is ASP or GLU;
- Y is GLY, VAL, LEU, norLEU, PHE, ILE, LYS, GLN, GLU, or ALA;
- Z is ##STR11## D is H or 1 or 2 substituents which increase the acidity of the phenol proton;
- E is H or C.sub.1 -C.sub.3 loweralkyl;
- R.sup.1 is OH or NH.sub.2.
6 more elements
Dependencies are inferred from the claim text.