Self-association properties of HPMA copolymers containing an amphipathic heptapeptide.

摘要: Receptor-binding peptides are suitable targeting moieties for macromolecular therapeutics. Binding several to one macromolecule may improve biorecognition due the multivalency effect. On other hand, resulting amphipathic structure of such conjugates result in association side-chains with a concomitant decrease accessibility side-chain-bound ligands. Using one-bead one-compound combinatorial method, we have recently identified heptapeptide (YILIHRN; HP) ligand CD21 receptor (Biomacromolecules 7, 3037, 2006). Here, evaluated relationship between and self-association N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-HP using fluorescence resonance energy transfer (FRET) evaluate their conformation solution. In addition HP, HPMA copolymers containing terminating tryptophan (energy donor) dansyl acceptor) were synthesized, solutions an excitation wavelength 295 nm (ratio emission intensity 510 nm/370 indicated efficiency). It was found that higher HP content correlated FRET efficiency, indicating formation compact coils. Modification copolymer backbone by incorporation acrylic acid (AA) comonomer units resulted decreased presumably expansion polymer coils as electrostatic repulsion. The dependence efficiency on pH agreement ionization profile AA residues. To determine effect enzymatic drug release kinetics, GFLG doxorubicin (DOX) incubated papain free DOX monitored. When increased above particular threshold, rate copolymer-GFLG-DOX-HP conjugates. data well hydrodynamic volumes determined size exclusion chromatography (SEC), molecular weights light scattering, kinetics release.