Characterization of natural-sequence recombinant human growth hormone

Abstract

Improved understanding of bacterial physiology in recent years has permitted novel approaches to the biosynthesis of recombinant proteins in general, and of human growth hormone (hGH) in particular. Originally, plasmid constructions for hGH synthesis coded for a 192- residue protein consisting of the natural 191 amino acid sequence preceded by an N-terminal methionine residue. This additional amino acid was a necessity of direct protein expression in Escherichia coli(Goeddel et al. 1979). The protein thus expressed and purified has been shown to be structurally and functionally very similar to the pituitary- derived hormone, and considerable clinical experience has shown methionyl -hGH (mhGH) to be a safe and effective therapeutic agent (see Fryklund et al. 1986 for a review). However, understanding of the mechanism by which bacteria secrete proteins has now made it feasible to produce a secreted recombinant hGH having the 191-residue “natural” sequence (Gray et al. 1984).