Duncan R, Cable H C, Rejmanová P, Kopecek J, Lloyd J B
Biochim Biophys Acta. 1984 May 25;799(1):1-8. doi: 10.1016/0304-4165(84)90320-9.
N-(2-Hydroxypropyl)methacrylamide ( HPMA ) copolymers have been proposed as a potential lysosomotropic drug delivery system. HPMA copolymers bearing tyrosinamide residues, bound either directly to the polymer backbone or via a glycylglycine spacer, were radiolabelled with [125I]iodide and the effect of tyrosinamide content on their rate of pinocytic uptake by rat visceral yolk sacs cultured in vitro was measured. Incorporation of tyrosinamide enhanced uptake of the copolymer, most markedly at substitutions above 10 mol%. 2,4-Dinitrophenol, an inhibitor of pinocytosis, was used to confirm that tissue association of 125I-radiolabelled copolymer was due to pinocytic uptake. The side-chain -Gly-Gly-Tyr-NH2 was degraded following the internalization of copolymers containing this spacer and degradation was partially sensitive to the lysosomal thiol-proteinase inhibitor leupeptin. It is postulated that the effect of tyrosinamide residues is to increase the hydrophobicity of poly( HPMA ) and thus to increase its capacity for nonspecific adsorptive pinocytosis.
N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物已被提议作为一种潜在的溶酶体亲和性药物递送系统。带有酪氨酸酰胺残基的HPMA共聚物，要么直接连接到聚合物主链上，要么通过甘氨酰甘氨酸间隔基连接，用[125I]碘进行放射性标记，并测定酪氨酸酰胺含量对其被体外培养的大鼠内脏卵黄囊胞饮摄取速率的影响。酪氨酸酰胺的掺入增强了共聚物的摄取，在取代度高于10摩尔%时最为明显。用胞饮作用抑制剂2,4-二硝基苯酚来证实125I放射性标记共聚物与组织的结合是由于胞饮摄取。含有这种间隔基的共聚物内化后，侧链-Gly-Gly-Tyr-NH2会降解，且这种降解对溶酶体硫醇蛋白酶抑制剂亮肽素部分敏感。据推测，酪氨酸酰胺残基的作用是增加聚（HPMA）的疏水性，从而提高其非特异性吸附胞饮的能力。
