Next-generation disulfide stapling: reduction and functional re-bridging all in one.
نویسندگان
چکیده
Herein we present a significant step towards next-generation disulfide stapling reagents. A novel class of reagent has been designed to effect both disulfide reduction and functional re-bridging. The strategy has been applied to great success across various peptides and proteins. Moreover, application to a multi-disulfide system resulted in functional re-bridging without disulfide scrambling.
منابع مشابه
Next-generation disulfide stapling: reduction and functional re-bridging all in one† †Electronic supplementary information (ESI) available: 1H and 13C NMR spectra for all small molecules, LC-MS, SDS-PAGE gels and UV-Vis analysis (where applicable) for all bioconjugates. See DOI: 10.1039/c5sc02666k Click here for additional data file.
Advances in protein modication by chemical means have led to the development of a range of protein bioconjugation methodologies. These methodologies have been successfully applied to a number of elds such as the uorescent tagging of proteins, the development of therapeutic protein conjugates to treat indications such as HIV, cancer and malaria, and for use as diagnostic tools. Whilst a large...
متن کاملFunctional native disulfide bridging enables delivery of a potent, stable and targeted antibody-drug conjugate (ADC).
Herein we report the use of next generation maleimides (NGMs) for the construction of a potent antibody-drug conjugate (ADC) via functional disulfide bridging. The linker has excellent stability in blood serum and the ADC, armed with monomethyl auristatin E (MMAE), shows excellent potency and cancer cell selectivity in vitro.
متن کاملSynthesis of Zinc Dimethyldithiocarbamate by Reductive Disulfide Bond Cleavage of Tetramethylthiuram Disulfide in Presence of Zn2+
The zinc(II) complex [Zn2(dmdtc)2(μ-dmdtc)2] has been synthesized directly from thiram ligand, containing a disulfide bond {dmdtc = N,N-dimethyldithiocarbamate; thiram = N,N-tetramethylthiuram disulfide}, and characterized by elemental analysis and spectroscopic methods. Surprisingly thiram, undergoes a reductive disulfide bond scission upon reaction with Zn2+ in methanolic media to give the [Z...
متن کاملNext generation maleimides enable the controlled assembly of antibody–drug conjugates via native disulfide bond bridging† †Electronic supplementary information (ESI) available: Synthetic procedures, 1H and 13C NMR spectra for synthesised compounds, additional SDS-PAGE gels, LCMS chromatograms, Ellman's analysis and other supplementary results. See DOI: 10.1039/c4ob01550a Click here for additional data file.
The advent of Adcetris™ and Kadcyla™, two recently FDA-approved antibody-drug conjugates (ADCs), in the clinic has had a major impact on the treatment of lymphoma and breast cancer patients, respectively, worldwide. Despite these successes many new ADCs fail at various stages of development, often due to shortcomings in the methods used for their assembly. To address this problem we have develo...
متن کاملAryloxymaleimides for cysteine modification, disulfide bridging and the dual functionalization of disulfide bonds.
Tuning the properties of maleimide reagents holds significant promise in expanding the toolbox of available methods for bioconjugation. Herein we describe aryloxymaleimides which represent 'next generation maleimides' of attenuated reactivity, and demonstrate their ability to enable new methods for protein modification at disulfide bonds.
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Chemical science
دوره 7 1 شماره
صفحات -
تاریخ انتشار 2016