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.