S. Asayama et al., SYNTHESIS OF NOVEL POLYAMPHOLYTE COMB-TYPE COPOLYMERS CONSISTING OF APOLY(L-LYSINE) BACKBONE AND HYALURONIC-ACID SIDE-CHAINS FOR A DNA CARRIER, Bioconjugate chemistry, 9(4), 1998, pp. 476-481
Citations number
40
Categorie Soggetti
Chemistry Inorganic & Nuclear",Biology,"Biochemical Research Methods",Chemistry
The polyampholyte comb-type copolymers consisting of a poly(L-lysine)
(PLL) main chain, a DNA binding site, and hyaluronic acid (HA) side ch
ains, cell-specific ligands, have been prepared as the DNA carrier tar
geting sinusoidal endothelial cells of liver. The reducing end of HA a
nd E-amino groups of PLL were covalently coupled by reductive aminatio
n to obtain the resulting comb-type copolymers (PLL-graft-HA). The cha
in length of HA was controlled by the enzymatic hydrolysis of high-mol
ecular weight HA. Since HA formed polyion complexes with PLL, the coup
ling reaction was carried out with high-ionic strength media to suppre
ss polyion complex formation. The reaction proceeded in a homogeneous
system, leading to a high efficiency of coupling (>70%) of HA onto the
PLL backbone. By using the enzymatic hydrolysis of HA and the reducti
ve amination reaction between HA and PLL with high-ionic strength medi
a, it is possible to prepare the various comb-type copolymers with a d
efined density and a defined length of HA side chains. Furthermore, we
also find that these polyampholyte comb-type copolymers vary their as
sembling structure in water in response to two kinds of environmental
factors, i.e., ionic strength and pH. Finally, a H-1 NMR study reveals
that the PLL backbone efficiently interacts with DNA molecules despit
e the presence of HA side chains having negative charges.