Boc-Protected Proline-Containing Monoamines as Promising Prodrugs

Abstract

In recent years, drug designers have increasingly focused on creating complex compounds containing biologically active molecules of various chemical classes in their structure. Such modifications increase the stability of resulting molecules in the organism and increase their ability to achieve the desired targeting effect. Regulatory peptides-based drugs are of particular interest. In this work, we combined the monoamines (serotonin or dopamine) and N-terminal-protected biologically active peptides or amino acids in a single compound and characterized the resulting molecules' enzymatic stability and possible molecular activity. Boc-Pro-5HT and Вос-Pro-DA were stable for at least 180 min of incubation in the presence of PEP, amino-and carboxy-peptidases, as well as blood plasma. This time is enough to reach their corresponding biological targets in the organism and become additional monoamines and regulatory peptides. It was also shown that these complex compounds possess specific targets on cell plasmatic membranes and can affect some neuroreceptor systems (GABA and Ach, in particular) as highly selective allosteric modulators. The above features make these molecules promising candidates for prodrugs and require further research on the mechanisms of their action.