Biosynthesis of regulatory peptides — evolutionary aspects

  • J. Michael Conlon


Neurohormonal peptides, in common with most peptides/proteins that are designated for export from the cell, are synthesized as higher-molecular-weight precursors which usually have no or reduced biological activity. The conversion to the mature secreted forms of the peptides involves limited proteolysis and frequently post-translational modifications to individual amino acid residues. Determination of a biosynthetic pathway requires a collaboration between the molecular biologist and the protein chemist. The primary structure of the primary gene product (preprohormone) is now determined, almost without exception, indirectly from the nucleotide sequence of cloned DNAs complementary to the mRNA directing synthesis of the hormone or from the nucleotide sequence of a cloned segment of DNA containing the gene isolated from an appropriate genomic library. In order to construct a processing pathway, it is necessary to isolate from a natural source the hormone and the other peptide fragment derived from the precursor and to determine their primary structures. Amino acid sequence analysis is usually carried out using the technique of automated gas-phase Edman degradation. Post-translational modification to individual amino acids may be identified most readily using the technique of fast-atom bombardment mass spectrometry. A comparison of the predicted structure of the preprohormone with the observed structures of the major peptide fragments derived from the precursor enables the identification of the sites of proteolytic cleavage.


Pancreatic Polypeptide Coho Salmon Regulatory Peptide Processing Site Fast Atom Bombardment Mass Spectrometry 
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  • J. Michael Conlon

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