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SpyTag is a 13-amino acid peptide (AHIVMVDAYKPTK) derived from the CnaB2 domain of the fibronectin-binding protein FbaB from Streptococcus pyogenes (Zakeri et al., 2012, PNAS). It is engineered to react spontaneously and irreversibly with its partner protein, SpyCatcher, through the formation of a covalent isopeptide bond between an aspartic acid side chain on the tag and a lysine side chain on the catcher (Li et al., 2014, Structure). While not a therapeutic target in the classical sense, SpyTag serves as a robust platform for protein engineering and vaccine development, enabling the modular assembly of complex structures like virus-like particles (VLPs) (Bruun et al., 2018, ACS Nano). In clinical applications, the technology is used to link antigens to scaffolds to enhance immune responses, as demonstrated in several COVID-19 vaccine candidates (Rahikainen et al., 2021, Angewandte Chemie). The system's high stability across various temperatures and pH levels makes it a versatile tool for creating complex bioconjugates and synthetic organelles in both research and therapeutic contexts (Sutherland et al., 2018, Chemical Science).
Spontaneous autocatalytic formation of an intermolecular isopeptide bond between the Asp117 residue of SpyTag and the Lys31 residue of SpyCatcher (Zakeri et al., 2012).
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