Determining intracellular degradation of cell-permeable substance, useful e.g. for optimizing properties of vaccinating peptides, by measuring concentration of degradation products

摘要

Determining intracellular degradation of a cell-permeable substance (I) comprises adding (I) to a medium being used to grow cells and measuring the accumulation of degradation products (II) of (I). Independent claims are also included for the following: (1) pharmaceutical composition comprising (I) that has been shown by the new method to undergo insignificant or significant intracellular degradation; (2) improving the pharmacokinetic properties of (I) by elucidating the structure responsible for degradation and then modifying the point of attack within this structure by molecular modeling; (3) identifying inhibitors (III) of intracellular degradation of (I) by including a test inhibitor in the growth medium; and (4) determining the mechanism of intracellular degradation of (I) by adding a known inhibitor, characterized by substrate specificity, to the test medium.