Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three analogues of bovine parathyroid hormone (bPTH), [Tyr-34]bPTH-(1--34) amide, [Nle-8,Nle-18,Tyr-34]bPTH-(1--34)amide, and [Nle-8,Nle-18, o-NPS-Trp-23,Tyr-34]bPTH-(1--34)amide were synthesized by the solid-phase method. The synthetic peptides were found to be homogeneous in multiple analytical systems. These analogues represent the NH2-terminal one-third of the hormone, previously shown to contain all the structural requirements necessary for biological activity, but containing several structural modifications associated with enhancement and stabilization of biological activity. When tested in the in vitro renal adenylylcyclase assay, in which unsubstituted bPTH-(1--34) has a potency of 5400 MRC Units/mg, [Tyr-34]bPTH-(1--34)amide had a potency of 16,1000 MRC Units/mg, [Nle-8,Nle-18,Tyr-34]bPTH-(1--34)amide was 10,100 MRC Units/mg, and [Nle-8,Nle-18,o-NPS-Trp-23,Tyr-34]bPTH-(1--34)amide was 10,600 MRC Units/mg. The diverse structural features incorporated in these hormone analogues, resulting in a several-fold increase in biological activity in vitro, demonstrate additive effects on biological activity and should prove valuable in certain biological applications, as well as in the design of other parathyroid hormone analogues of enhanced potency.
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PMID:Design and synthesis of parathyroid hormone analogues of enhanced biological activity. 56 Sep 53

Fresh frozen bovine parathyroid glands were defatted in acetone, when extracted with phenol. Following trichloroacetic acid precipitation, the resultant peptides were chromatographed on Sephadex G-100. Parathyroid hormone (BPTH) characteristically elutes in the fourth peak. However, we also observed significant hormonal activity, both biological and immunological, in the fifth elution peak. The peak V material had potent hypercalcemic activity in the rat and chick, and stimulated adenylate cyclase activity in the rat renal cortex bioassay. This material was further purified by ion exchange chromatography on carboxymethylcellulose in 8 M urea. The biological activity of the purified peptide (3700 MRC units/mg) was equivalent to that of the native hormone on a molar basis. Amino acid analysis, carboxypeptidase digestion, and partial Edman sequence analysis identified this material as BPTH 1-65, a hormonal fragment lacking the C-terminal 19 residues of the 84 residue hormone molecule. Several immunoassays using different anti-PTH antisera had variable reactivity toward the BPTH 1-65 fragment, showing that it may be useful for further characterizing antibody recognition sites. The presence of a lysine residue at position 65 suggests a tryptic-like cleavage may be responsible for the genesis of this hormonal fragment. Further investigation will be necessary to determine if this peptide has physiological significance.
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PMID:A biologically active hormonal fragment isolated from bovine parathyroid glands (BPTH 1-65). 114 77