Human somatotropin: Semisynthesis of the hormone by noncovalent interaction of the natural NH 2-terminal fragment with a synthetic analog of the COOH-terminal fragment

Abstract

Complementation of the natural [Cys (Cam) 53]-HGH-(1–134) fragment with synthetic analogs of COOH-terminal fragments of human somatotropin (HGH), namely [Nle 170, Ala 165,182]-HGH-(140–182) and [Nle 170,Ala 165,182]-HGH-(140–187) has been investigated. It was found that the synthetic fragment, [Nle 170,Ala 165,182]-HGH-(140–187), gave a recombinant with about 40% HGH radioreceptor-binding activity. When compared with the natural recombinant, the semisynthetic hormone exhibited similar receptor-binding activities. The natural and semisynthetic recombinants were indistinguishable in radioimmunoassay. The α-helical content of the semisynthetic recombinant was completely restored in comparison with that of the native hormone as revealed by circular dichroism spectra. On the other hand, attempts to obtain a recombinant with the synthetic [Nle 170,Ala 165,182]-HGH-(140–182) were unsuccessful. The synthesis of [Nle 170,Ala 165,182]-HGH-(140–182) and [Nle 170,Ala 165,182]-HGH-(140–187) is herein described.