The insulin is a peptide hormone, secreted by the pancreas, first discovered in 1922 by Banting and Macleod . This is a small protein containing 51 amino acids (17 of the proteinogenic amino acids), composed of 2 polypeptide chains: A and B. Chain A contains 21 amino acids and these are forming two small α-helixes between A1–A7 and A12–A18 residues. The main medication of the diabetes is the insulin; the active form is the insulin monomer, which is an instable molecule, because the long storage time, or the high temperature, can cause the monomer insulin to adapt an alternative fold, rich in β-sheets, which is pharmaceutically inactive. The aim of this study is to form different insulin complexes with all the cyclodextrin used for pharmaceutical excipients (native cyclodextrin, methyl, hydroxyethyl, hydroxypropyl and sulfobutylether substituted β-cyclodextrin), in silico condition, with the AutoDock molecular modeling program, to determine the best type of cyclodextrin or cyclodextrin derivate to form a complex with an insulin monomer, to predict the molar ratio, the conformation of the complex, and the intermolecular hydrogen bonds formed between the cyclodextrin and the insulin. From the results calculated by the AutoDock program it can be predicted that insulin can make a stable complex with 5–7 molecules of hydroxypropyl-β-cyclodextrin or sulfobutylether-β-cyclodextrin, and by forming a complex potentially can prevent or delay the amyloid fibrillation of the insulin and increase the stability of the molecule.
Bucur, P.; Fülöp, I.; Sipos, E. Insulin Complexation with Cyclodextrins—A Molecular Modeling Approach. Molecules 2022, 27, 465. https://doi.org/10.3390/molecules27020465