Chemoenzymatic Synthesis of Polypeptides for Use as Functional and Structural Materials

Abstract

Polypeptides inspired by the natural functional and structural proteins present in living systems are promising materials for various fields in terms of their versatile functionality and physical properties. Designing and synthesizing mimetic sequences of specific peptide motifs in proteins are important for exploring the functionality of natural proteins. Chemoenzymatic polymerization, which utilizes aminolysis (i.e., the reverse reaction of hydrolysis catalyzed by proteases), is a useful technique for synthesizing artificial polypeptide materials and has several advantages, including facile synthesis protocols, environmental friendliness, scalability, and atom economy. In this review, recent progress in chemoenzymatic polypeptide synthesis for the production of functional and structural materials for various applications is summarized in conjunction with the current status of technical challenges in the field.

Chemical Synthesis of Silk-Mimetic Polymers

“…Synthesis of peptide prepolymers for step-growth polymerization is typically achieved using stepwise amino acid coupling, which is relatively time-consuming and repetitive, or NCA ROP, which requires the use of toxic phosgene derivatives, organic solvents, and stringent reaction conditions to achieve peptides with low dispersity [113,114]. Chemoenzymatic polymerization is considered a "green synthetic method", as reactions can be conducted in aqueous solvents with non-toxic bioderived reagents [115,116]. Moreover, chemoenzymatic polymerization overcomes the problem of epimerization by using enzyme catalysts with high reaction specificity.…”

Periodic introduction of aromatic units in polypeptides via chemoenzymatic polymerization to yield specific secondary structures with high thermal stability

“…This reaction is a tandem reaction, including rearrangement to form amide bonds, which allows broad structural variations of the N-substituent of the amide groups. As another example, chemoenzymatic synthesis using proteases is a green method to synthesize various polypeptide materials [17]. Aminolysis reactions of amino acid esters catalyzed by proteases proceed under kinetically controlled conditions, resulting in polypeptide formation with excellent regio-and stereoselectivity.…”

Poly(alanine-nylon-alanine) as a bioplastic: chemoenzymatic synthesis, thermal properties and biological degradation effects

“…8 On the other hand, chemoenzymatic polymerizations have emerged as a superior method over other solution-based syntheses because of their eco-friendly nature. [9][10][11] These facile approaches use mild aqueous media, are atom economical reactions, and are scalable to industrial size. 12 We have developed various polypeptides, which include not only homopolymers but also random copolymers containing several amino acid residues.…”