63128-51-8Relevant articles and documents
Isonitrile induced bioorthogonal activation of fluorophores and mutually orthogonal cleavage in live cells
Li, Jie,Li, Lin,Mao, Wuyu,Shen, Guohua,Su, Dunyan,Wu, Haoxing,Xu, Hui,Zhang, Xiaoyang
supporting information, p. 573 - 576 (2022/02/01)
Fluorophores with different emission wavelengths were efficiently quenched by a tert-butyl terminated tetrazylmethyl group and activated by an isonitrile–tetrazine click-to-release reaction. Nucleic acid templated chemistry significantly accelerated this
Photo Cross-Linking Probes Containing ?-N-Thioacyllysine and ?-N-Acyl-(δ-aza)lysine Residues
B?k, Michael,Chakladar, Saswati,Laursen, Jonas S.,Madsen, Julie L. H.,Martín-Gago, Pablo,Olsen, Christian A.
supporting information, (2020/03/11)
Posttranslational modifications (PTMs) are important in the regulation of protein function, trafficking, localization, and marking for degradation. This work describes the development of peptide activity/affinity-based probes for the discovery of proteins that recognize novel acyl-based PTMs on lysine residues in the proteome. The probes contain surrogates of ?-N-acyllysine by introduction of either hydrazide or thioamide functionalities to circumvent hydrolysis of the modification during the experiments. In addition to the modified PTMs, the developed chemotypes were analyzed with respect to the effect of peptide sequence. The photo cross-linking conditions and subsequent functionalization of the covalent adducts were systematically optimized by applying fluorophore labeling and gel electrophoresis (in-gel fluorescence measurements). Finally, selected probes, containing the ?-N-glutaryllysine and ?-N-myristoyllysine analogues, were successfully applied for the enrichment of native, endogenous proteins from cell lysate, recapitulating the expected interactions of SIRT5 and SIRT2, respectively. Interestingly, the latter mentioned was able to pull down two different splice variants of SIRT2, which has not been achieved with a covalent probe before. Based on this elaborate proof-of-concept study, we expect that the technology will have broad future applications for pairing of novel PTMs with the proteins that target them in the cell.
Bisubstrate inhibitors of nicotinamide N-methyltransferase (NNMT) with enhanced activity
Gao, Yongzhi,Van Haren, Matthijs J.,Moret, Ed E.,Rood, Johannes J. M.,Sartini, Davide,Salvucci, Alessia,Emanuelli, Monica,Craveur, Pierrick,Babault, Nicolas,Jin, Jian,Martin, Nathaniel I.
, p. 6597 - 6614 (2019/08/20)
Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide to form N-methylnicotinamide. Overexpression of NNMT is associated with a variety of diseases, including a number of cancers and metabolic disorders, suggesting a role for NNMT as a potential therapeutic target. By structural modification of a lead NNMT inhibitor previously developed in our group, we prepared a diverse library of inhibitors to probe the different regions of the enzyme's active site. This investigation revealed that incorporation of a naphthalene moiety, intended to bind the hydrophobic nicotinamide binding pocket via π-πstacking interactions, significantly increases the activity of bisubstrate-like NNMT inhibitors (half-maximal inhibitory concentration 1.41 μM). These findings are further supported by isothermal titration calorimetry binding assays as well as modeling studies. The most active NNMT inhibitor identified in the present study demonstrated a dose-dependent inhibitory effect on the cell proliferation of the HSC-2 human oral cancer cell line.
