Self-association of cholesteryl-bearing poly(L-lysine) in water and control of its secondary structure by host-guest interaction with cyclodextrin

A cholesteryl-bearing poly(L-lysine) (CHPLL) was synthesized by the condensation reaction of cholesteryl N-(6-isocyanatehexyl) carbamate with poly(L-lysine) (PLL). Sonicated samples of CHPLLs, which were substituted by 0.8, 3.4, and 5.4 cholesteryl groups per 100 lysine units, gave a single peak after sufficient ultrasonication by high-performance liquid column chromatography. The particle sizes (RG) and aggregation numbers (N), which were determined by static light scattering, increased with an increase in the DS of cholesterol in CHPLL (R-G = 16-22 nm, N = 1.3-4.2). These CHPLLs form an ct-helical structure at a lower pH compared to the parent PLL by circular dichroism spectroscopy. The partial modification of PLL by hydrophobic cholesteryl groups leads to the formation of hydrogel nanoparticles by their self-association, and this induces the alpha-helical structure of PLL. This a-helicity can be controlled by the degree of substitution of cholesteryl groups. The helical content of CHPLL decreased upon the addition of beta-cyclodextrins, which were complexed with cholesteryl groups and reached a value similar to that of unmodified PLL. The secondary structure of CHPLL was controlled by host-guest interaction with cyclodextrin.