Relationship between isoelectric point of native and chemically modified insulin and liposomal fusion

Abstract

Native insulin causes fusion of negatively charged liposomes in the pH range from 3.0 to 5.5. In marked contrast, insulin with all three amino groups succinylated did not show fusion ability at any pH. On the other hand, insulin amidated with glycine methyl ester with all six carboxyl groups blocked shifted its activity to higher pH, showing a pH range of activity from 3.0 to 7.4. When the carboxyl groups were recovered by hydrolysis of methoxyl groups from glycine methyl ester-treated insulin, the protein obtained (glycyl-insulin with six free carboxyl groups) behaved as native insulin. A good correlation between the isoelectric point values of insulin and its derivatives and their fusion properties was found.

Nanodiamond–insulin complexes as pH-dependent protein delivery vehicles

“…Charged amino acid residues on the exterior of the insulin molecule contribute to its hydrophilicity and can be attracted to the ND surface. Although the isoelectric point of insulin is approximately 5.6 [43], indicating a slightly negative net charge at neutral pH, the electrostatic interactions and H-bonding between ND functional groups and biomolecules with amine groups may lead to attractive interactions. Fig.…”