albumin binding ligands and albumin conjugate uptake by cancer cells白蛋白结合配体和白蛋白共轭吸收癌细胞.pdfVIP

Frei Diabetology Metabolic Syndrome 2011, 3:11 DIABETOLOGY /content/3/1/11 METABOLIC SYNDROME REVIEW Open Access Albumin binding ligands and albumin conjugate uptake by cancer cells Eva Frei Abstract The scope of this short review is to summarise the knowledge gleaned from the fate of drugs transported by albumin upon contact with the target cancer cell or cells in inflamed tissues. The authors expertise covers covalently bound drugs and their cellular uptake and release from albumin. This review therefore aims to deduce what will happen to drugs such as insulin detemir which is considered to bind non-covalently to albumin and may have a fate similar to fatty acids transported by albumin. Keywords: Insulin detemir, aminofluorescein-albumin, methotrexate-albumin, clathrin-heavy-chain, lysosomes, fatty acids Introduction fatty acids, steroids and drugs. These are bound to dis- Insulin detemir was developed as a long acting drug to tinct hydrophobic pockets in the albumin molecule, achieve a continuous and steady blood level of insulin which has a very rigid and stable three dimensional rather than the peaks achieved with postprandial injec- structure due to 17 S-S bonds. In addition albumin con- tions of conventional insulin. The molecule was modi- tains very few aromatic amino acids but many amino fied by eliminating Thr 30 and adding a C14 fatty acid acids with functional groups like amino and carboxyl (myristic acid) by a chemically