Design and synthesis of a new polymer drug delivery conjugate.
This work describes the design and synthesis of a novel polymer conjugate to facilitate intracellular release of attached cargo. Water soluble poly[N(2-hydroxypropyl) methacrylamide] with derivatizable pendant side chains was used as the polymer carrier. The membrane active Tat peptide was masked with poly(ethylene glycol) to inhibit non-specific interactions with exterior cell membranes, and then covalently linked to poly[N-(2-hydroxypropyl) methacrylamide]. A novel heterobifunctional crosslinker was synthesized containing both maleimide and aldehyde functionality to allow attachment of peptides to the polymer backbone through a pH sensitive bond. Analysis of the proposed conjugate by gel permeation chromatography, nuclear absorbance spectroscopy, and absorbance measurements indicate that the desired compound has been synthesized.
Christie
R J
RJ
Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA.
Findley
D J
DJ
Grainger
D W
DW
D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D015696:Gene Products, tat / Q000008:administration & dosage* / Q000737:chemistry*; D008422:Materials Testing; D008968:Molecular Conformation; D008970:Molecular Weight; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding; D012995:Solubility
D000178:Acrylamides; D004337:Drug Carriers; D015696:Gene Products, tat; D011108:Polymers; C045985:methacrylamide