Development of Efficient Chemistry to Generate Site-Specific Disulfide-Linked Protein- and Peptide-Payload Conjugates: Application to THIOMAB Antibody-Drug Conjugates was written by Sadowsky, Jack D.;Pillow, Thomas H.;Chen, Jinhua;Fan, Fang;He, Changrong;Wang, Yanli;Yan, Gang;Yao, Hui;Xu, Zijin;Martin, Shanique;Zhang, Donglu;Chu, Phillip;dela Cruz-Chuh, Josefa;ODonohue, Aimee;Li, Guangmin;Del Rosario, Geoffrey;He, Jintang;Liu, Luna;Ng, Carl;Su, Dian;Lewis Phillips, Gail D.;Kozak, Katherine R.;Yu, Shang-Fan;Xu, Keyang;Leipold, Douglas;Wai, John. And the article was included in Bioconjugate Chemistry in 2017.Formula: C6H8N2O2S This article mentions the following:
Conjugation of small mol. payloads to specific cysteine residues on proteins via a disulfide bond represents an attractive strategy to generate redox-sensitive bioconjugates, which have value as potential diagnostic reagents or therapeutics. Advancement of such “direct-disulfide” bioconjugates to the clinic necessitates chem. methods to form disulfide connections efficiently, without byproducts. The disulfide connection must also be resistant to premature cleavage by thiols prior to arrival at the targeted tissue. We show here that commonly-employed methods to generate direct disulfide-linked bioconjugates are inadequate for addressing these challenges. We describe our efforts to optimize direct-disulfide conjugation chem., focusing on the generation of conjugates between cytotoxic payloads and cysteine-engineered antibodies (i.e., THIOMAB antibody-drug conjugates, or TDCs). This work culminates in the development of novel, high-yielding conjugation chem. for creating direct payload disulfide connections to any of several Cys mutation sites in THIOMAB antibodies or to Cys sites in other biomols. (e.g., human serum albumin and cell-penetrating peptides). We conclude by demonstrating that hindered direct disulfide TDCs with two Me groups adjacent to the disulfide, which have heretofore not been described for any bioconjugate, are more stable and more efficacious in mouse tumor xenograft studies than less hindered analogs. In the experiment, the researchers used many compounds, for example, Ethyl 2-mercapto-1H-imidazole-4-carboxylate (cas: 64038-64-8Formula: C6H8N2O2S).
Ethyl 2-mercapto-1H-imidazole-4-carboxylate (cas: 64038-64-8) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. The pharmacophore of imidazole exists in bioactive compounds including amino acids, plant growth regulators and therapeutic agents.n increase of the alkyl chain length of the alcohols. Formula: C6H8N2O2S
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem