Fully convergent chemical synthesis of ester insulin: determination of the high resolution X-ray structure by racemic protein crystallography.

ABSTRACT: Efficient total synthesis of insulin is important to enable the application of medicinal chemistry to the optimization of the properties of this important protein molecule. Recently we described "ester insulin"--a novel form of insulin in which the function of the 35 residue C-peptide of proinsulin is replaced by a single covalent bond--as a key intermediate for the efficient total synthesis of insulin. Here we describe a fully convergent synthetic route to the ester insulin molecule from three unprotected peptide segments of approximately equal size. The synthetic ester insulin polypeptide chain folded much more rapidly than proinsulin, and at physiological pH. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin (i.e., [Asp(B10), Lys(B28), Pro(B29)]ester insulin) w

SUBMITTER: Avital-Shmilovici M 

PROVIDER: S-EPMC3625376 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature