Kyotorphin analogues - transport and enzymatic stability studies with computational methods

Peptide exhibiting a biological effect once inside the body undergoes multiple biotransformations leading to their inactivation and degradation. An effective way for its use is the introduction into the body simultaneously with peptidase inhibitors. Another viable approach is the development of peptide mimetics that exhibit the same or increased biological effect, but increased stability. Here we present the docking studies of kyotorphin analogues with already known in vivo biological effect regarding aminopeptidases and oligopeptide transporters. The objective was to determine whether these analogues exert their pronged effect due to their stability to the peptidases action and also whether they can be transported by the transmembrane transporters which also influence their effects. The docking results showed that kyotorphin analogues can not be hydrolyzed by aminopeptidase N and only three of them can be transported through the cell membrane. From these studies it was concluded that the tested analogues are effective, stable, and do not affect overall metabolism, which makes them suitable for the treatment of pain.