On October 15-16, 2023, the WRC2023 Biorthogonal and Click Chemistry Academic Conference took place in Shanghai. The event, initiated and hosted by the World Leading Scientists Association (WLA), and organized by the World Leading Scientists International Joint Laboratory (WLA Labs), was chaired and addressed by Prof. K. Barry Sharpless, Nobel laureate in Chemistry in 2001 and 2022, and Prof. Kuiling DING, President of Shanghai Jiao Tong University and member of the Chinese Academy of Sciences (CAS). Prof. Michael Levitt, Nobel laureate in Chemistry in 2013, delivered the opening speech on behalf of the organizers.

Nobel laureate Prof. K. Barry Sharpless and CAS academician Prof. Benzhong TANG jointly presented the award to Wenhui GAO.

The conference featured an academic poster selection event, soliciting high-quality academic posters from universities and research institutions nationwide. Expert reviewers in relevant fields conducted professional evaluations of the posters, considering factors such as discipline, research progress, innovation, significance, and layout design. In the end, among over fifty submissions, the work titled "Covalently Engineered Affibody-Molecular glue Conjugate for Proximity-Enabled Reactive Therapeutics" by Wenhui GAO, a Ph.D candidate from the School of Chemistry and Chemical Engineering at Shanghai Jiao Tong University, stood out, earning the sole first prize for excellent academic posters. Nobel laureate Prof. K. Barry Sharpless and CAS academician Prof. Benzhong TANG jointly presented the award to Wenhui GAO. 

Posters are not merely decorative backdrops; they play a significant role at the conference. During the event, high-standard academic posters from Shanghai Jiao Tong University, Fudan University, Tsinghua University, Peking University, ShanghaiTech University, Shanghai University, Westlake University, and institutes affiliated with CAS were showcased. These posters garnered attention from many scientists, earning praise for their academic quality and innovation. During the tea break, prominent scientists and young researchers actively participated in enthusiastic discussions revolving around the posters.

Introduction to the Prize-Winning Work

Title: Covalently Engineered Affibody-Molecular glue Conjugate for Proximity-Enabled Reactive Therapeutics

Strategy：Based on the previous concept of antibody-drug conjugates and the therapeutic potential of protein-degrading targeted chimeras (PROTACs), this work involves a site-specific sulfonyl fluoride group into an affinity protein Z_HER2:342 and develops a covalent affinity protein-protein degrader conjugate that can covalently bind to the target HER2 protein through SuFEx click chemistry for active targeted therapy in HER2-overexpressing cancers. The covalent binding strategy avoids the reversible dynamic binding between traditional antibodies and antigens, imparting long-lasting binding capabilities to the affinity protein-protein degrader conjugate and addressing issues related to the poor pharmacokinetic performance due to the small molecular weight of affinity proteins. Covalent binding improves the delivery efficiency of PROTACs and increases the bio-safety of the drug.

Figure 1. Structure and Delivery Mechanism of Z_HER2:342-36_FSY-CR8.

a) Structure of Z_HER2:342-36_FSY-CR8. b) Crystal Structure of Z_HER2:342-HER2-ECD (PDB：3MZW). c) Schematic Diagram of the Covalently Binding of Z_HER2:342-36_FSY-CR8 and HER2-ECD: During the binding process, the sulfonyl fluoride group at position 36 of the affinity protein gradually approaches the position 490 histidine in HER2-ECD, thereby triggering a SuFEx click reaction to form a covalent bond.

Translator: Chenyun SUN

Reviser: Xiaoke HU