Targeted Peptides

Chimeric peptides' ability to enter the cell and cell organelles is primarily interesting as the ability to deliver targeted peptides.

Control and synchronization of events in the process of cell division is realised by a large complex of molecules. One of the key players in this process are the cyclins, activating the so-called cyclin-dependent kinase (CDK). During the cell cycle first a sequential activation of specific transcription of cyclin  takes place and then an active complex of cyclin-CDK is formed. The cell division in the control (restriction) points (G1, S, G2) can be stopped by inhibiting the relevant cyclin complex through specific proteins. A family of proteins that inhibit cyclin D (control transition G1-S) belong to proteins INK4a.
 
R16INK4a protein is one of the most studied in this group. It is shown that this protein inhibits the activity of CDK4 and CDK6, in the complex with cyclin D, which prevents phosphorylation of pRb and release of E2F, and leads to cell cycle breach at the G1-S border crossing. Structural and functional studies of the protein revealed an active fragment of p16INK4a (amino acids 84-103), which is responsible for the inhibition of CDK4 and CDK6, in the complex with cyclin D.
 
Another example - the protein p53, controlling cell division breaches in response to genotoxic effects in the G2 phase, and activating apoptosis in case of irreversible damages.
 
These proteins are a group of gene products, that dysfunction is often associated with a tumor. Most of them tend to interact with the formation of macromolecular complexes, leading to inhibition or activation of the corresponding proteins and functions.
 
One of the current trends in the study of these proteins has been to identify the minimal peptide sequence that can perform a function of full-length protein. This way, of the protein inhibiting cell proliferation, leading to a halt cell division at G1 phase and responsible for the cell differentiation and aging (p16) a peptide moderating the features of full-length protein was isolated.
 
Now MetaMax is conducting the scientific research that could create a family of molecules - drug candidates with a more predictable pharmacokinetic characteristics, improved safety profile and less expensive synthesis.