Current strategies and perspectives in insulin gene therapy for diabetes

Chistiakov, Dimitry A.; Tyurina, I

doi:10.1586/17446651.2.1.27

Cited by 1 publication

(1 citation statement)

References 62 publications

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“…The chain evolves into proinsulin by cutting out the signal peptide. Then, proinsulin needs to be cleaved into insulin (an A chain and B chain) by removing the C-peptide linking the two chains [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Structural Analysis of Recombinant Human Preproinsulins by Structure Prediction, Molecular Dynamics, and Protein-Protein Docking

Jung¹,

Kim²,

Lee³

et al. 2017

Genomics Inform

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More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several in silico simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.

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Section: Introductionmentioning

confidence: 99%