Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1995-05-08
1999-07-06
Russel, Jeffrey E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 13, 530324, 530325, 530326, 530358, A61K 3803, A61K 3810, A61K 3816, C07K 1400
Patent
active
059197617
ABSTRACT:
Less toxic agents for reversal of heparin or low molecular weight heparin anticoagulation which are synthetic protamine-like polycationic peptides having a total cationic charge which is less than that of n-protamine. In preferred embodiments, arginine residues of n-protamine are replaced with lysine residues for ease of manufacture. Selective positively charged arginine residues have been replaced with an uncharged amino acid residue or its analog, such as glycine or glutamine, in order to reduce the total sequences of 29 and 32 amino acid residues wherein 4 to 5 clusters of 2 to 4 positively charged amino acids are separated by 2 to 6 neutral amino acids. The C-terminus and the N-terminus can be modified to mitigate against in vivo degradation by carboxypeptidases and aminopeptidases. Another modification, specifically use of .alpha.-helix forming amino acids, such as glutamic acid, further promotes anticoagulation reversal. A still further modification includes the incorporation of a cell adhesion ligand, such as the RGD sequence, into the synthetic protamine-like polycationic peptide.
REFERENCES:
patent: 4792525 (1988-12-01), Ruoslahti et al.
patent: 5272261 (1993-12-01), Cardin et al.
patent: 5358934 (1994-10-01), Borovsky et al.
patent: 5534619 (1996-07-01), Wakefield
patent: 5614494 (1997-03-01), Wakefield et al.
patent: 5721212 (1998-02-01), Wakefield et al.
Eur. J. Biochem, vol. 158, Issued 1986, McKay et al., "Rainbow Trout Protamines", pp. 361-366.
Journal of Vascular Surgery, vol. 18, No. 1, Issued 1993, DeLucia et al., "Efficacy and Toxicity of Differently Charged Polycatonic Protamine-like Peptides," pp. 49-60.
Andrews Philip C.
Stanley James C.
Wakefield Thomas W.
Monsanto Raphael A.
Rohm Benita J.
Russel Jeffrey E.
The Board of Regents of the University of Michigan
LandOfFree
Peptides for heparin and low molecular weight heparin anticoagul does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Peptides for heparin and low molecular weight heparin anticoagul, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Peptides for heparin and low molecular weight heparin anticoagul will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-899044