Supramolecular assembly of Cp1-11 peptide and insulin for rapid-acting formulation

Abstract

In order to improve the life quality of diabetic patients, it is very important to develop rapid-acting insulin formulations that can mimic the physiological meal-time secretion profile of insulin in healthy people. Although several insulin analogues have been designed to provide postprandial glycemic control, still there are some serious disadvantages. A supramolecular strategy is presented here to inhibit insulin aggregation and improve its bioactivity by using Cp1-11 peptide. As a fragment of C-peptide in proinsulin, Cp1-11 peptide was found to influence insulin oligomerization by supramolecular interactions. This work demonstrates that the Cp1-11 peptide can interact with oligomeric insulin and facilitate its disaggregation into the physiologically active monomeric form. Computer simulation indicates that Cp1-11 can insert into the space between the C-terminal tail and the N-terminal helix of the B-chain of insulin, causing dissociation of the insulin dimer. The supramolecular assembly of Cp1-11 and insulin can improve the bioavailability and therapeutic effect of insulin on the control of in vivo blood glucose levels. These results suggest that Cp1-11 peptide can modulate the intermolecular interaction of aggregated insulin and prevent the transition from monomeric to multimeric states, and shows great potential for the development of an effective rapid-acting strategy to treat diabetes.