Contemporary chemical protein synthesis has been dramatically advanced over the past few decades, which has enabled chemists to reach the landscape of synthetic biomacromolecules. Chemical synthesis can produce synthetic proteins with precisely controlled structures which are difficult or impossible to obtain via gene expression systems. Herein, we summarize the key enabling ligation technologies, major strategic developments, and some selected representative applications of synthetic proteins and provide an outlook for future development.

Acinetobacter baumannii exhibits resistance to most first-line antibiotics; thus, development of new antibacterial agents is urgently required. Pseudaminic acid exists as the surface glycan of A. baumannii . In this study, we chemically synthesized pseudaminic acid, conjugated it to carrier protein CRM197 using the OPA ( ortho -phthalaldehyde) chemistry, and obtained three Pse–CRM197 conjugates with different Pse loadings. These Pse–CRM197 conjugates were found to stimulate high immune responses in mice, which protected the vaccinated mice from infections caused by Pse-producing A. baumannii . Our data indicate that chemically synthesized Pse–CRM197 conjugates can be developed into vaccines against Pse-bearing pathogens, thus offering a feasible alternative for the control of clinical infections caused by multidrug-resistant (MDR) A. baumannii , for which current treatment options are extremely limited.

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