Mittwoch, 30. November 2016

cell-penetrating peptides (CPP)

The peptides in question are called  cell-penetrating peptides (CPP) and were developed by for example Jonathan McMurray and his research team at Kennesaw State University. McMurray took a viral protein fragment (from HIV) or another special tailored synthetic peptide  and attached it to Calmodulin, a human protein. What they made was a peptide that carries and delivers other drugs into cells. Yes, into. Not like the other carriers that never drop their deliveries. This peptide couples with the cells does its delivery and then leaves again. Which means none of the drugs go to waste, and you milk every mg of peptide you can from your dose.

a) The higher extracellular pH deprotonates fatty acids attracting arginine rich peptides.

b) The positively charged guanidinium groups bind strongly to the deprotonated carboxyl groups of fatty acids.

c) The positive charge of the peptides is now screened by the fatty acids. This allows the peptides to get efficiently inserted in the core of the plasma membrane. This insertion destabilizes the plasma membrane nucleating a transient toroidal pore.

d) The peptide diffuses on the surface of this pore towards the interior of the cell while the lower pH in the cytosol protonates the fatty acids releasing the peptide.

e) The peptide gets released and the transient pore becomes unstable and closes.

f) The protonated (and neutral) fatty acids rapidly flip-flop across the plasma membrane eventually becoming in contact with the extracellular media at higher pH where they become negatively charged and the process can start again.