Abstract
Polymerisation of α-amino acid N-carboxyanhydrides (NCAs) is one of the most common techniques to prepare synthetic polypeptides. Of special interest are the NCAs derived from α-amino acids, L-aspartic acid and L-glutamic acid, since most investigations have been focused on their use to synthesise multiblock copolypeptides or hybrid synthetic polypeptide-polymers to design excipients suitable for delivery of bioactive compounds. This perspective highlights advantages of using L-aspartic acid and L-glutamic over other natural α-amino acids in that their pendant carboxyl group serves as a reactive handle for coupling a variety of reactive groups, and because the resulting polypeptides have the ability to adopt secondary structures. In addition, recent progress in the ring-opening polymerisation of NCAs will be discussed. Throughout, we provide representative examples that shed light on the NCAs polymerisation process, and we finally share our perspectives concerning the practical use of anionic α-amino acids as building blocks for future investigations.
Highlights
Natural proteins, which are ubiquitous and essential for the structure and function of cells, tissues and organs, the transport of molecules, and the catalysis of biochemical reactions that are needed to sustain cellular processes, are constituted from 20 naturally occurring amino acids [1]
Of special interest are the NCAs derived from α-amino acids, L-aspartic acid and L-glu tamic acid, since most investigations have been focused on their use to synthesise multiblock copolypeptides or hybrid synthetic polypeptide-polymers to design excipients suitable for delivery of bioactive compounds
Three main techniques are employed for the synthesis of polypeptides: ring-opening polymerisation (ROP) of α-amino acid N-carboxyanhydrides (NCAs) [6], solid phase peptide synthesis (SPPS) [7] and protein biosynthesis [8]; the former enables the production of high molecular weight (MW) polypeptides with narrow dispersities in a facile manner [6]
Summary
Natural proteins, which are ubiquitous and essential for the structure and function of cells, tissues and organs, the transport of molecules, and the catalysis of biochemical reactions that are needed to sustain cellular processes, are constituted from 20 naturally occurring amino acids [1]. AAA provide the following advantages: i) the feasibility to polymerise some amino acid ester NCAs like γ-benzyl-L-glutamate NCA (BLG-NCA) and β-benzyl-L-aspartate NCA (BLA-NCA) in solution is driven by the good solubility of the resulting polymers in most organic solvents (e.g. dimethylformamide (DMF), chloroform, and dichloromethane (DCM)) [18], ii) long chains with low dispersity can merely be obtained from soluble and mostly helix-forming peptides [e.g. poly(γ-alkyl-L-gluta mate) and poly(Nε-benzyloxycarbonyl-L-lysine)] [19], iii) the inherent COOH functionality in AAA, from an organic chemistry point of view, serves as a reactive handle for coupling a variety of reactive groups or even pre-formed polymers that are orthogonal to NCA polymerisation, leading to a library of side-chain-modified NCAs (SCM NCAs) [20], iv) synthetic polypeptides of AAA derivatives exhibit transitions be tween α-helical and random coil conformations This phenomenon oc curs because their secondary structures are sensitive to temperature and especially to pH variations. We discuss the principal advantages of using AAA as building blocks in the design of PBCs to build novel excipients for the delivery of bioactive compounds, and we share our perspectives for their use in future investigations
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