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Solid-phase synthesis and biologic activity of human parathyroid hormone (1-84)
N A Goud1, R L McKee, M K Sardana
1Bachem, Inc., Torrance, California.
Summary
Chemically synthesized human parathyroid hormone (hPTH) is now available in large quantities. This highly pure synthetic hPTH (1-84) demonstrates potent biologic activity, paving the way for further research.
Area of Science:
- Biochemistry
- Endocrinology
- Peptide Chemistry
Background:
- Parathyroid hormone (PTH) is crucial for calcium and phosphate homeostasis.
- Previous synthesis methods yielded limited quantities of human parathyroid hormone (hPTH).
Purpose of the Study:
- To chemically synthesize full-length human parathyroid hormone (hPTH) on a large scale.
- To confirm the authenticity and evaluate the biologic activity of synthetic hPTH (1-84).
Main Methods:
- Solid-phase peptide synthesis using the Merrifield technique.
- Purification via high-performance liquid chromatography (HPLC).
- Authenticity confirmed by Edman degradation and tryptic digestion.
Main Results:
- Successfully synthesized >100 mg of >96% pure synthetic hPTH (1-84).
- Synthetic hPTH (1-84) exhibited high potency in PTH receptor binding (Kb = 1-25 nM).
- Demonstrated potent stimulation of adenylate cyclase activity (Km = 1-14 nM).
Conclusions:
- Significant quantities of synthetic hPTH (1-84) are now available for extensive research.
- The synthetic hormone enables detailed in vitro and in vivo studies of its biologic properties.
- Facilitates the evaluation of parathyroid hormone antagonists.