Stimuli‐Triggered Sol–Gel Transitions of Polypeptides Derived from α‐Amino Acid N‐Carboxyanhydride (NCA) Polymerizations

Abstract

The past decade has witnessed significantly increased interest in the development of smart polypeptide-based organo- and hydrogel systems with stimuli responsiveness, especially those that exhibit sol-gel phase-transition properties, with an anticipation of their utility in the construction of adaptive materials, sensor designs, and controlled release systems, among other applications. Such developments have been facilitated by dramatic progress in controlled polymerizations of α-amino acid N-carboxyanhydrides (NCAs), together with advanced orthogonal functionalization techniques, which have enabled economical and practical syntheses of well-defined polypeptides and peptide hybrid polymeric materials. One-dimensional stacking of polypeptides or peptide aggregations in the forms of certain ordered conformations, such as α helices and β sheets, in combination with further physical or chemical cross-linking, result in the construction of three-dimensional matrices of polypeptide gel systems. The macroscopic sol-gel transitions, resulting from the construction or deconstruction of gel networks and the conformational changes between secondary structures, can be triggered by external stimuli, including environmental factors, electromagnetic fields, and (bio)chemical species. Herein, the most recent advances in polypeptide gel systems are described, covering synthetic strategies, gelation mechanisms, and stimuli-triggered sol-gel transitions, with the aim of demonstrating the relationships between chemical compositions, supramolecular structures, and responsive properties of polypeptide-based organo- and hydrogels.

Synthesis and gelation of copolypept(o)ides with random and block structure

“…In contrast, PSar displays no detectable CP by turbidity measurements below 100°C and is miscible with water at all ratios . As we observed gelation of random copolypept(o)ides at room temperature, its formation mechanism could be completely different from the previously suggested micellar percolation or fibrillar entanglement . In Figure , we proposed the possible gelation mechanism for PSar‐ co ‐PIGA and PSar‐ b ‐PIGA.…”

Multi-responsive polypeptide hydrogels derived from N-carboxyanhydride terpolymerizations for delivery of nonsteroidal anti-inflammatory drugs

“…The entanglement of nanofibrils resulting from long range interactions, including peptide–peptide interaction and PEG-PEG association, constructs the three-dimensional networks of this polypeptide hydrogel system. 55 …”

“…Conversion of the longer nanofibrils into short nanofibrils and spherical aggregates, which lacked long range connectivity, resulted in the breakdown of the hydrogel networks. 55 When the sol was heated to 37 °C for over 1 h, reformation of the longer nanofibrils reconnected the hydrogel networks (Scheme 2). …”

Synthesis and Properties of Shape Memory Poly(γ-Benzyl-l-Glutamate)-b-Poly(Propylene Glycol)-b-Poly(γ-Benzyl-l-Glutamate)

“…Currently, ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs) has been the most common method used for large scale preparation of high molecular weight polypeptides [18]. Many stimuli-responsive polypeptides have been prepared by the ROP of α-amino acid NCAs based on the conformational transitions between secondary structures [21][22][23][24]. However, there are few reports on shape memory polypeptide.…”