Poly(Ethylene Glycol)-Based Backbones with High Peptide Loading Capacities

Abstract

Polymer-peptide conjugates are a promising class of compounds, where polymers can be used to overcome some of the limitations associated with peptides intended for therapeutic and/or diagnostic applications. Linear polymers such as poly(ethylene glycol) can be conjugated through terminal moieties and have therefore limited loading capacities. In this research, functionalised linear poly(ethylene glycol)s are utilised for peptide conjugation, to increase their potential loading capacities. These poly(ethylene glycol) derivatives are conjugated to peptide sequences containing representative side-chain functionalised amino acids, using different conjugation chemistries, including copper-catalysed azide-alkyne cycloaddition, amide coupling and thiol-ene reactions. Conjugation of a sequence containing the RGD motif to poly(allyl glycidyl ether) by the thiol-ene reaction, provided a conjugate which could be used in platelet adhesion studies.

Synthesis of allyl end‐block functionalized poly(ε‐caprolactone)s and their facile post‐functionalization via thiol–ene reaction

“…It is worth noting that side reactions such as the polymerization of AGE proceeded via the activated chain end mechanism or a reaction between an activated AGE and moisture, resulting in homopoly(AGE) byproduct, might not be completely excluded . Unreacted AGE and poly(AGE) byproduct are soluble in methanol, and thereby could be removed by multiple precipitation in methanol. Accordingly, for a relatively low feed AGE to PCL‐diol molar ratio (3.1–20.0), 1 H NMR analysis of the purified product indicated that the number of allyl groups incorporated into a PCL chain was slightly lower than the theoretical value (Entries 1–6, Table ).…”

Glycidyl Triazolyl Polymers: Poly(ethylene glycol) Derivatives Functionalized by Azide–Alkyne Cycloaddition Reaction

“…The utilization of the copolymer containing allyl glycidyl ether is a promising way of achieving this goal (Figure ). [4a,5b,29] The allyl group can react with an appropriate cross‐linker by olefin metathesis, thiol–ene chemistry, and acetal formation. [35,36,5b] (4) There is a need to further develop GTPs for biomedical applications.…”

“…[35,36,5b] (4) There is a need to further develop GTPs for biomedical applications. Devocelle and co‐workers failed to prepare oligopeptide‐functionalized GTPs . Looking for a good reaction condition of Cu(I)‐catalyzed AAC for introducing the biomolecules is an important issue to be solved.…”

“…Devocelle and co-workers failed to prepare oligopeptide-functionalized GTPs. [29] Looking for a good reaction condition of Cu(I)-catalyzed AAC for introducing the biomolecules is an important issue to be solved. The utilization of a ligand for stabilizing the Cu(I) catalyst, [37] for example, tris(3-hydroxypropyl-triazolylmethyl)amine, [37b] is a possible solution.…”

Responsive hybrid (poly)peptide–polymer conjugates

“…An N-terminal cysteine was added to the RGD sequence, which was subsequently reacted with PAGE, although the peptide conjugation to PAGE was reportedly low. 145 In one study, a peptide sequences based on the CDR H3 region of IgG1 b12, a neutralizing anti-HIV-1 antibody, was conjugated to the side chains of a poly(pentafluorophenyl methacrylate) (PPFMA) via heat initiated thiol-ene chemistry. Though the conjugate system was not as effective as the IgG1 b12 antibody by itself, the platform shows potential as an interesting therapeutic alternative.…”