Avian (chicken) parathyroid hormone: synthesis and comparative biological evaluation of the 1-34 fragment.
The full-length amino acid sequence of the avian (chicken) form of parathyroid hormone (cPTH) has recently been elucidated. We have chemically synthesized, purified to a high degree, and analytically and biologically characterized the N-terminal 1-34 fragment of the avian hormone. The biological properties of cPTH-(1-34)NH2 were evaluated and compared to the bovine fragment bPTH-(1-34) in several assays. The potency of cPTH-(1-34)NH2 in binding to PTH receptors, in stimulating adenylate cyclase activity and in relaxing smooth muscle tissue was approximately one-tenth that of bPTH-(1-34). Comparison of the avian sequence to other native PTH related sequences suggests that changes in the binding domain of the 1-34 active fragment may account for the decline in potency.
Caulfield
M P
MP
Department of Biological Research and Molecular Biology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Levy
J J
JJ
McKee
R L
RL
Goldman
M E
ME
DeHaven
P A
PA
Reagan
J E
JE
Heaney
L
L
Nutt
R F
RF
Winquist
R J
RJ
Russell
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001681:Biological Assay; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002645:Chickens / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology*; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D000596:Amino Acids; D010281:Parathyroid Hormone; D010446:Peptide Fragments; C025076:parathyroid hormone (1-34), bovine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases