Biomimetic synthesis of lispro insulin via a chemically synthesized "mini-proinsulin" prepared by oxime-forming ligation.

ABSTRACT: Here we report a proof-of-principle study demonstrating the efficient folding, with concomitant formation of the correct disulfides, of an isolated polypeptide insulin precursor of defined covalent structure. We used oxime-forming chemical ligation to introduce a temporary "chemical tether" to link the N-terminal residue of the insulin A chain to the C-terminal residue of the insulin B chain; the tether enabled us to fold/form disulfides with high efficiency. Enzymatic removal of the temporary chemical tether gave mature, fully active insulin. This chemical tethering principle could form the basis of a practical, high yield total synthesis of insulin and analogues.

SUBMITTER: Sohma Y 

PROVIDER: S-EPMC3690821 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature