Site-specific Bioconjugation and Convergent Click Chemistry Enhances Antibody-Chromophore Conjugate Binding Efficiency.

ABSTRACT: Photosensitizer (PS)-antibody conjugates (photoimmunoconjugates, PICs) enable cancer cell-targeted photodynamic therapy (PDT). Nonspecific chemical bioconjugation is widely used to synthesize PICs but gives rise to several shortcomings. The conjugates are heterogeneous, and the process is not easily reproducible. Moreover, modifications at or near the binding sites alter both binding affinity and specificity. To overcome these limitations, we introduce convergent assembly of PICs via a chemo-enzymatic site-specific approach. First, an antibody is conjugated to a clickable handle via site-specific modification of glutamine (Gln) residues catalyzed by transglutaminase (TGase, EC 2.3.2.13). Second, the modified antibody intermediate is conjugated to a compatible chromophore via click chemistr

SUBMITTER: Sadiki A 

PROVIDER: S-EPMC7386253 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature