title: Two novel bovine somatotropin species generated from a common dehydroalanine intermediate.
abstract: Under stressed conditions such as prolonged exposure to high pH, the C-terminal disulfide bridge in bovine somatotropin (bST) is susceptible to a base catalyzed beta-elimination reaction. This reaction converts the disulfide bond to a dehydroalanine residue with loss of a sulphur atom. Two altered species were isolated in pure form and determined to be generated from this dehydroalanine intermediate. One is a monomeric lanthionyl bST (L-bST) with a thioether linkage, and the other is an inter-molecular disulfide linked dimer containing a lysinoalanine. These two novel structures were unambiguously determined using various techniques including enzymatic digestion, amino acid sequencing and analysis, and mass spectrometry. The monomeric L-bST was demonstrated to be equipotent to normal bST in a hypox rat assay, thus showing that formation of lanthionine in place of this disulfide bond does not affect it bioactivity.
authors.affiliation: Global Chemistry R&D, Monsanto, 800 N. Lindbergh Blvd, St. Louis, MO 63167, USA. jacob.s.tou@monsanto.com
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Tou
authors.forename: Bernard N
authors.initials: BN
authors.lastname: Violand
authors.forename: Zi Yi
authors.initials: ZY
authors.lastname: Chen
authors.forename: James A
authors.initials: JA
authors.lastname: Carroll
authors.forename: Michael R
authors.initials: MR
authors.lastname: Schlittler
authors.forename: Kamal
authors.initials: K
authors.lastname: Egodage
authors.forename: Simon
authors.initials: S
authors.lastname: Poruthoor
authors.forename: Carol
authors.initials: C
authors.lastname: Lipartito
authors.forename: Darrell A
authors.initials: DA
authors.lastname: Basler
authors.forename: Judy W
authors.initials: JW
authors.lastname: Cagney
authors.forename: S Bradley
authors.initials: SB
authors.lastname: Storrs
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002852:Chromatography, Ion Exchange; D013006:Growth Hormone / Q000737:chemistry* / Q000302:isolation & purification; D006863:Hydrogen-Ion Concentration; D008241:Lysinoalanine / Q000737:chemistry; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D011487:Protein Conformation; D055503:Protein Multimerization; D020539:Sequence Analysis, Protein; D013440:Sulfides / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D013440:Sulfides; D008241:Lysinoalanine; C073294:growth hormone, bovine; D013006:Growth Hormone; C015102:dehydroalanine; C001520:lanthionine; D000409:Alanine