Stability-enhanced variants of parathyroid hormone

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Glycoprotein – e.g. – mucins – proteoglycans – etc.

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

530324, 514 2, 514 8, 514 12, C07K 300, A61K 3702, A61K 3700, A01N 3718

Patent

active

053826582

ABSTRACT:
Herein described are variants of parathyroid hormone that retain significant PTH activity and are substantially resistant to trypsin and trypsin-like enzymes. The variants are useful pharmaceutically, to treat bone disorders such as osteoporosis and in other therapeutic applications. Specific embodiments of the invention include [His.sup.25 ]PTH and [His.sup.25 His.sup.26 Leu.sup.27 ]PTH.

REFERENCES:
patent: 4423037 (1983-12-01), Rosenblatt et al.
patent: 4698328 (1987-10-01), Neer et al.
patent: 4761406 (1988-08-01), Flora et al.
patent: 4968669 (1990-11-01), Rosenblatt et al.
Reppe et al, "Characterization of a K26Q Site-Directed Mutant Of Human Parathyroid Hormone Expressed In Yeast", J. Biol. Chem., 266:14198-14201, (1991).
Rosenblatt et al., "Modification Of The Arginines In Parathyroid Hormone: Effect On Biological Activity," Biochemistry, 17:3188, (1978).
Rodan et al, "Factors Associated With Humoral Hypercalcemia Of Malignancy Stimulate Adenylate Cyclase In Osteoblastic Cells", J. Clin. Invest., 72:1511-1515, (1983).
Rabbani et al, "Influence Of The Amino-Terminus On in Vitro and in Vitro Biological Activity Of Synthetic Parathyroid Hormone-Like Peptides Of Malignancy", 123:2709-2716, (1988).
Kimura et al, "Solution Synthesis Of [ASN.sup.76 ]-Human Parathyroid Hormone (1-84)", Biochem. Biophys. Res. Comm., 114:493-499 (1983).
Keutmann, "Current Research On Calcium Regulating Hormones", University of Texas Press, pp. 57-63, (1987).
Rosenblatt et al, "Chemical And Biological Properties Of Synthetic, Sulfur-free Analogues Of Parathyroid Hormone", J. Biol. Chem., 251:159-164, (1976).
Fairwell et al, "Total Solid-Phase Synthesis, Purification, and Characterization Of Human Parathyroid Hormone-(1-84)", Biochemistry, 22:2691, (1983).
Goud et al, "Solid-Phase Synthesis And Biologic Activity Of Human Parathyroid Hormone (1-84)", J. Bone Min. Res., 6(8):781-789, (1991).
Wosnick et al, "Total Chemical Synthesis And Expression in Escherichia coli Of A aize Glutathione-Transferase (GST) Gene", Gene, 76:153-160, (1989).
Barnett et al, "Rapid Generation Of DNA Fragments By PCR Amplification Of Crude, Synthetic Oligonucleotides", Nucl. Acids Res., 18(10):3094 (1990).
Hendy et al, "Nucleotide Sequence Of Cloned cDNAs Encoding Human Preproparathyroid Hormone", Proc. Natl. Acad. Sci. U.S.A., 78:7365-7369, (1981).
Kunkel T., "Rapid And Efficient Site-Specific Mutagenesis Without Phenotypic Selection", Proc. Natl. Acad. Sci. USA, 82:488-492, (1985).
Higuchi et al, "A General Method Of in vitro Preparation And Specific Mutagenesis Of DNA Fragments: Study Of Protein And DNA Interactions", Nucl. Acids Res., 16:7351-7367, (1988).
Sarkar et al, "The Megaprimer Method Of Site-Directed Mutagenesis", Biotechniques, 8(1):404-407, (1990).
Rabbani et al, "Synthesis And Characterization Of Extended And Deleted Recombinant Analogues Of Parathyroid Hormone-(1-84): Correlation Of Peptide Structure With Function", Biochemistry, 29:10080-10089.
Laemmli, "Cleavage Of Structural Proteins During The Assembly Of The Head Of Bacteriophage T4", Nature, 227:680-685, (1970).
Schagger et al, "Tricine-Sodium Dodecyl Sulfate-Polacrylamide Gel Electrophoresis For The Separation Of Proteins In The Range From 1 to 100 kDa", Analytical Biochemistry, 166:368-379, (1987).
Reeve et al.; Anabolic Effect of Human Parathyroid Hormone Fragment on a Trabecular Bone in Involutional Osteoporosis: A Multicentre Trial; British Medical Journal (7 Jun. 1980) pp. 1340-1344.
Mosekilde et al.; The Anabolic Effects of Human Parathyroid Hormone (hPTH) on Rat Vertebral Body Mass Are also Reflected in the Quality of Bone, Assessed by Biomechanical Testing: A Comparison Study between hPTH-(1-34) and hPTH-(1-84); The Endocrine Society (vol. 129, No. 1).

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Stability-enhanced variants of parathyroid hormone does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Stability-enhanced variants of parathyroid hormone, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Stability-enhanced variants of parathyroid hormone will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-747653

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.