アルギニンペプチドの生体膜透過機構に関する物理化学的研究

抄録

Arginine–rich peptides directly penetrate into cells across cell membranes via spontaneous energy–independent process. We demonstrated that interaction of arginine–rich peptides with sulfated glycosaminoglycans (GAGs) at the cell surface plays a critical role in their cell membrane penetrations: the high–affinity binding of arginine–rich peptides to GAGs is driven by favorable enthalpy contributions, resulting in the efficient cell membrane penetration. The enthalpy gain is possibly derived from a unique property of the guanidino group in arginine to form multidentate hydrogen bonding with sulfate and carboxylate groups of GAGs. Such GAG interaction can be accompanied with charge neutralization of arginine–rich peptides, promoting their cell membrane penetration. Taken together with our finding that arginine–rich peptides cross the lipid membranes through membrane perturbation, a mechanism for the cell membrane penetration has been proposed: the mechanism involves (1) binding to GAG at the cell surface, followed by (2) the transfer to the cell membrane and (3) the entry into cytosol.