STRUCTURAL CHARACTERIZATION OF THE 2 REFOLD DIMERS OF RECOMBINANT BOVINE SOMATOTROPIN (BST)

Two major dimers are generated during the folding/oxidation of inclusi on bodies of recombinant bovine somatotropin (bST). These dimers repre sent the major part of the inactive high molecular weight species that are formed in this process. The structures of the two dimers are unam biguously determined by peptide mapping using trypsin, thrombin cleava ge, and selective DTT reduction experiments. Results indicate that the formation of both dimers involves the large disulfide loop cysteines. The latter-eluting dimer from RP-HPLC, previously reported as a large loop concatenated dimer, was revised to be an antiparallel disulfide- linked dimer. On the other hand, the first eluting dimer is a concaten ane in which two monomers are held together by the interlocking of the two large disulfide loops.