Isolation and characterization of a sulfoxide and a desamido derivative of biosynthetic human growth hormone.
Two derivatives of biosynthetic human growth hormone, a sulfoxide and a mixture of two monodesamido isomers, have been isolated and characterized. The sulfoxide derivative arises from an oxidation of Met-14. The major site of deamidation is at Asn-149 with a minor site at Asn-152. In addition, a fraction has been isolated from a sample of human growth hormone that was maintained at 40 degrees C for 2 weeks. This fraction, the isolated impurities fraction, contains the sulfoxide and the desamido forms, thereby demonstrating that these derivatives are the primary degradation products of biosynthetic human growth hormone. The sulfoxide, the desamido, and the isolated impurities fraction exhibit full biological activity.
Becker
G W
GW
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Tackitt
P M
PM
Bromer
W W
WW
Lefeber
D S
DS
Riggin
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D005260:Female; D013006:Growth Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007016:Hypophysectomy; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins
D011994:Recombinant Proteins; C058601:somatotropin sulfoxide; D013006:Growth Hormone