Atom Transfer Radical Polymerization with Polypeptide Initiators: A General Approach to Block Copolymers of Sequence‐Defined Polypeptides and Synthetic Polymers

Abstract

Summary: A novel two‐step polymerization strategy allowing the integration of sequence‐defined oligopeptides into synthetic polymers has been demonstrated by the successful synthesis of an oligopeptide‐block‐poly(n‐butyl acrylate) copolymer. The approach utilizes a solid‐phase supported synthesis of an oligopeptide macroinitiator (SPPS) followed by solution‐phase atom transfer radical polymerization (ATRP) initiated by the oligopeptide macroinitiator. The resulting block copolymer exhibited a low $\overline M _{\rm w} /\overline M _{\rm n}$ (1.19) and a controllable $\overline M _{\rm n}$.Poly(n‐butyl acrylate)‐block‐oligopeptide.imagePoly(n‐butyl acrylate)‐block‐oligopeptide.

Peptide conjugate hydrogelators

“…Both solution-phase and solid-phase amino acid coupling 100 techniques allow the construction of sequence specific peptides, unlike NCA polymerisation, which affords homopolypeptide blocks. Solution-phase is useful for short peptide blocks containing less than ten amino acid residues.…”

“…This is somewhat surprising since the method has been shown to be extremely effective for producing well-defined polymer-peptide conjugates. [100][101][102][103][104] For a comprehensive review on controlled polymerisation from 60 peptidic initiators (up to late 2006), the reader is directed to work by Haddleton and co-workers. 85 The only work known to us at this time which used this approach to produce polymer-peptide hydrogelators is that of Mei et al 105 The authors describe a conventional heterogeneous polymerisation 65 strategy whereby the peptidic initiator was bound to a solidsupport.…”

“…The two rheological criteria required for a gel are the independence of 95 the dynamic elastic (or storage) modulus (G′) on the oscillatory frequency, and that G′ exceeds the loss modulus (G″) by approximately one order of magnitude. 73 G′ is an indicator of the elastic behaviour and measures the ability to store deformation energy that can be recovered after removing 100 the load cycle. A number of different measurements can be carried out, including frequency sweeps and strain sweeps, where the behaviour of the gel at different frequencies or strains is measured.…”

Biological–synthetic hybrid block copolymers: Combining the best from two worlds

“…A very interesting divergent approach to the synthesis of protein/peptide-synthetic polymer hybrids was published recently by Börner et al 29 In contrast to the convergent strategies discussed earlier, which involve the grafting of PEG onto a protein or peptide, or the divergent liquid-phase method, in which the peptide is assembled in a stepwise fashion from a soluble synthetic polymer support, the method introduced by Börner et al is based on the controlled radical polymerization of vinyl monomers from a well-defined peptide fragment containing an appropriate initiator group. As shown in Scheme 7, the preparation of HIGHLIGHTthe hybrid block copolymers starts with solid-phase synthesis of the desired peptide fragment followed by on-bead acylation of the N-terminal glycine residue with 2-bromopropionic acid.…”

“…In combination with the N,N,NЈ,NЈ,NЉ-pentamethyldiethylenetriamine (PMDETA)/CuBr/CuBr 2 catalyst system, the oligopeptide-based initiator has been successfully used to initiate ATRP of n-butyl acrylate, yielding an oligopeptide-poly(n-butyl acrylate) block copolymer with a number-average molecular weight (M n ) of approximately 10.000 g/mol and a polydispersity (weight-average molecular weight/number-average molecular weight) of approximately 1.19. 29 Although the published example uses only a relatively small oligopeptide initiator and the polymerization of n-butyl acrylate is carried out in dimethyl sulfoxide as the solvent, this approach seems very promising and may be further extended to the modification of proteins with the retention of structure and function, as well. The basic tools for this are available.…”