Site-specific construction of triptolide-based antibody-drug conjugates

2021 ◽  
pp. 116497
Author(s):  
Ding Wei ◽  
Yurong Mao ◽  
Zili Xu ◽  
Jiakang Chen ◽  
Jiusheng Li ◽  
...  
Keyword(s):  
Site Specific ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Specific Construction ◽  
Antibody Drug

scholarly journals Site-Specific and Trigger-Activated Modification of Proteins by Means of Catalytic Hemin/G-quadruplex (hGQ) DNAzyme Nanostructures

2020 ◽  
Author(s):  
Jordi Keijzer ◽  
Bauke Albada
Keyword(s):  
Heavy Chain ◽  
Protein Modification ◽  
Site Specificity ◽  
Site Specific ◽  
Antibody Drug Conjugates ◽  
Synthetic Dna ◽  
Drug Conjugates ◽  
Sds Page ◽  
G Quadruplex ◽  
Antibody Drug

<div>Synthetic DNA that forms various G-quadruplex nanostructures, in combination with hemin, <i>N</i>-methyl luminol derivatives, and H2O2 can site-specifically modify proteins (i.e. evidence is provided for lysozyme and human alpha-thrombin). The catalytic modification is completed in 15-30 mins, and the site-specificity is influenced by the G-quadruplex topology (a total of 22 G-quadruplex forming sequences was tested). We also show that the heavy chain of the therapeutic antibody trastuzumab is modified, which facilitates the preparation of antibody-drug conjugates. Furthermore, a trigger can be programmed into this synthetic DNA so that the protein modification chemistry is made dependent on an external trigger.</div><div><br></div>Techniques used: HPLC, SDS-PAGE, LC-MS/MS, NMR.

Abstract 752: CovisoLinK: New bacterial transglutaminase Q-Tag substrate for the development of site specific antibody-drug conjugates

2018 ◽  
Author(s):  
Eva Sivado ◽  
Vincent Thomas ◽  
Meddy El Alaoui ◽  
Anne-Catherine Jallas ◽  
Mike R. Dyson ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Site Specific ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

Discovery of Pyrophosphate Diesters as Tunable, Soluble, and Bioorthogonal Linkers for Site-Specific Antibody–Drug Conjugates

2016 ◽  
Vol 138 (4) ◽  
pp. 1430-1445 ◽  
Author(s):  
Jeffrey C. Kern ◽  
Mark Cancilla ◽  
Deborah Dooney ◽  
Kristen Kwasnjuk ◽  
Rena Zhang ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Site Specific ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

scholarly journals Synthesis of site-specific antibody-drug conjugates by ADP-ribosyl cyclases

2020 ◽  
Vol 6 (23) ◽  
pp. eaba6752 ◽  
Author(s):  
Zhefu Dai ◽  
Xiao-Nan Zhang ◽  
Fariborz Nasertorabi ◽  
Qinqin Cheng ◽  
Jiawei Li ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Reaction Times ◽  
Single Step ◽  
Her2 Positive ◽  
Site Specific ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

Most of the current antibody-drug conjugates (ADCs) in clinic are heterogeneous mixtures. To produce homogeneous ADCs, established procedures often require multiple steps or long reaction times. The introduced mutations or foreign sequences may cause high immunogenicity. Here, we explore a new concept of transforming CD38 enzymatic activity into a facile approach for generating site-specific ADCs. This was achieved through coupling bifunctional antibody-CD38 fusion proteins with designer dinucleotide-based covalent inhibitors with stably attached payloads. The resulting adenosine diphosphate–ribosyl cyclase–enabled ADC (ARC-ADC) with a drug-to-antibody ratio of 2 could be rapidly generated through single-step conjugation. The generated ARC-ADC targeting human epidermal growth factor receptor 2 (HER2) displays excellent stability and potency against HER2-positive breast cancer both in vitro and in vivo. This proof-of-concept study demonstrates a new strategy for production of site-specific ADCs. It may provide a general approach for the development of a novel class of ADCs with potentially enhanced properties.

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