Oxidative refolding of insulin-like growth factor 1 yields two products of similar thermodynamic stability: A bifurcating protein-folding pathway

Can one protein sequence encode two structures? Oxidative folding of human insulin-like growth factor 1 (IGF- 1), a globular protein of 70 residues, is shown to yield two products of similar thermodynamic stability. This observation is of particular interest in light of the recent demonstration that two of the three disulfide bonds in native IGF-1 rearrange in the presence of dithiothreitol [Hober, S., et al. (1992) Biochemistry 31, 1749-1756]. Kinetics of the IGF-1 folding pathway were monitored by high- performance liquid chromatography (rp-HPLC). Disulfide-pairing schemes of intermediates and products were established by peptide mapping