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- Title
In Situ Self‐Assembly of Bispecific Peptide for Cancer Immunotherapy.
- Authors
Wang, Man‐Di; Lv, Gan‐Tian; An, Hong‐Wei; Zhang, Ni‐Yuan; Wang, Hao
- Abstract
Precise and effective manipulation of protein functions still faces tremendous challenges. Herein we report a programmable peptide molecule, consisted of targeting and self‐assembly modules, that enables specific and highly efficient assembly governed by targeting receptor proteins. Upon binding to the cell membrane receptor, peptide conformation is somewhat stabilized along with decreased self‐assembly activation energy, promoting peptide‐protein complex oligomerization. We first design a GNNQQNY‐RGD peptide (G7‐RGD) to recognize integrin αVβ3 receptor for proof‐of‐concept study. In the presence of αVβ3 protein, the critical assembly concentration of free G7‐RGD decreases from 525 to 33 μM and the resultant G7‐RGD cluster drives integrin receptor oligomerization. Finally, a bispecific assembling peptide antiCD3‐G7‐RGD is rationally designed for cancer immunotherapy, which validates CD3 oligomerization and concomitant T cell activation, leading to T cell‐mediated cancer cell cytolysis.
- Subjects
PEPTIDES; CELL receptors; T cells; ACTIVATION energy; IMMUNOTHERAPY; INTEGRINS; PROTEIN receptors
- Publication
Angewandte Chemie, 2022, Vol 134, Issue 10, p1
- ISSN
0044-8249
- Publication type
Academic Journal
- DOI
10.1002/ange.202113649