Extending Halogen-based Medicinal Chemistry to Proteins: IODO-INSULIN AS A CASE STUDY.

ABSTRACT: Insulin, a protein critical for metabolic homeostasis, provides a classical model for protein design with application to human health. Recent efforts to improve its pharmaceutical formulation demonstrated that iodination of a conserved tyrosine (Tyr^B26) enhances key properties of a rapid-acting clinical analog. Moreover, the broad utility of halogens in medicinal chemistry has motivated the use of hybrid quantum- and molecular-mechanical methods to study proteins. Here, we (i) undertook quantitative atomistic simulations of 3-[iodo-Tyr^B26]insulin to predict its structural features, and (ii) tested these predictions by X-ray crystallography. Using an electrostatic model of the modified aromatic ring based on quantum chemistry, the calculations suggested that the analog

SUBMITTER: El Hage K 

PROVIDER: S-EPMC5207135 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature