Cysteine‐Functional Polymers via Thiol‐ene Conjugation

Abstract

A thiofunctional thiazolidine is introduced as a new low-molar-mass building block for the introduction of cysteine residues via a thiol-ene reaction. Allyl-functional polyglycidol (PG) is used as a model polymer to demonstrate polymer-analogue functionalization through reaction with the unsaturated side-chains. A modified trinitrobenzenesulfonic acid (TNBSA) assay is used for the redox-insensitive quantification and a precise final cysteine content can be predetermined at the polymerization stage. Native chemical ligation at cysteine-functional PG is performed as a model reaction for a chemoselective peptide modification of this polymer. The three-step synthesis of the thiofunctional thiazolidine reactant, together with the standard thiol-ene coupling and the robust quantification assay, broadens the toolbox for thiol-ene chemistry and offers a generic and straightforward approach to cysteine-functional materials.

Side-Chain Cysteine-Functionalized Poly(2-oxazoline)s for Multiple Peptide Conjugation by Native Chemical Ligation

“…Synthesis and characterization of the thiofunctional cysteine derivative have been done as reported in detail elsewhere. 28 In brief, literature-known formation of the HCl-salt of Tz4CA by treatment of l -cysteine hydrochloric salt with acetone 34 was performed first, followed by formylation of the amine according to literature. 35 Subsequently, the carboxylic functionality was mildly activated using N , N -carbonyldiimidazole in chloroform for 2 h at room temperature under an inert atmosphere.…”

“…2,2-Dimethylthiazolidine-4-carboxylic acid (Tz4CA) was synthesized according to Woodward et al 34 2,2-Dimethylthiazolidin-3-( N -formyl)-4-carboxylic acid (FTz4CA) was prepared as reported before. 28 FTz4Cys was prepared according to Kuhlmann et al 28 using chloroform instead of DMF as solvent. Synthesis of BuOx and DecOx was prepared according to Gress et al 21 or Kempe et al 24 ( Supporting Information ).…”

Single addition of an allylamine monomer enables access to end-functionalized RAFT polymers for native chemical ligation

“…[20][21][22][23][24] To date NCL has only been reported on two occasions as a means to prepare functionalized polymers. 25,26 In these examples, synthetic processing of monomeric units within the polymer (postpolymerization) was required to incorporate cysteine moieties into the side-chains of the polymers for subsequent NCL-based derivatization (see Scheme 1A for a schematic representation).…”

“…25,26 Herein, we report the use of NCL chemistry, in combination with RAFT polymerization technologies, to generate end-functionalized peptide-polymer conjugates in an efficient manner. Specifically, we describe a simple and reliable procedure to insert a single unit of a protected allylamine monomer at the chain end of RAFT polymers.…”

Dispersity control of linear poly(glycidyl ether)s by slow monomer addition

“…1 Ethylene oxide (EO), ethoxy ethyl glycidyl ether (EEGE) and other oxirane-monomers have already been statistically or block copolymerized with allyl glycidyl ether (AGE) to improve functionalization options. [5][6][7] Side-reactions and their control in glycidyl ether polymerizations were investigated as this determines the applicability, i.e. via thiol-ene click chemistry) has allowed the synthesis of multifunctional PEOderivatives over the past decades.…”