Synthesis and Noncovalent Protein Conjugation of Linear-Hyperbranched PEG-Poly(glycerol) α,ω_n-Telechelics

Abstract

Linear-hyperbranched, heterobifunctional alpha,omega(n) telechelic block copolymers consisting of a linear poly(ethylene glycol) (PEG) chain and a hyperbranched polyglycerol (PG) block have been prepared in five steps, using a protected amino-functional initiator. The polyfunctionality omega(n) (OH groups) can be adjusted by the degree of polymerization (DP(n)) of the polyglycerol block. Subsequent introduction of a single biotin unit by amidation in alpha-position permitted noncovalent bioconjugation with avidin.

Self‐Assembly of Hyperbranched Polymers and Its Biomedical Applications

“…[ 136 ] To date, many supramolecular protein delivery systems have been developed to improve protein stability and reduce immunogenicity. [ 137 ] As mentioned in the above section, HBP assemblies and conjugates have been proved to be excellent drug delivery systems, thus they can also be used to deliver proteins.…”

“…Recently, Frey and coworkers synthesized a biotin conjugated linear-hyperbranched PEG-b -HPG heterotelechelics, and subsequently used it for avidin delivery. [ 136 ] HBP assemblies were also used to realize protein purifi cation and detection. Rimmer and coworkers prepared thermosensitive hyperbranched PNIPAM with imidazole end groups.…”

Noncovalent PEGylation via Lectin–Glycopolymer Interactions

“…[16][17][18][19][20][21][22][23][24][25][26] Examples include polymer conjugation via: co-factor reconstitution, 16 the biotin-streptavidin complex, 18 supramolecular complexation with cucurbituril, 19 charge-charge 20 and metal affinity 21,24 interactions, as well as lectin-mediated complexation. 25,27,28 The advantage of noncovalent systems is that temporal control of conjugate assembly and disassembly can be asserted by the presence of competitor molecules.…”

Hyperbranched aliphatic polyether polyols

“…130 By covalent attachment of a pyrene anchor to the focal amine, LHBCs based on PEG and hbPG have also been used to solubilize carbon nanotubes. 132 The use of cholesterol or other aliphatic glyceryl ethers as initiator resulted in unusual linear-hyperbranched lipids, which are suitable for liposome preparation and drug-delivery applications.…”

“…137 This method was further developed by Wurm et al by direct grafting of glycidol from a linear multihydroxy-functional PEG macroinitiator with short linPG FIGURE 25 Synthesis of LHBCs based on PEG and hbPG with variable structural parameters and single functional end groups using specific initiators. [129][130][131] HIGHLIGHT segments at both PEG ends (linPG-b-PEG-b-linPG). These materials are available over a broad range of molecular weights and with up to 300 end groups.…”