215654-55-0Relevant articles and documents
Aldehyde-mediated bioconjugation: Via in situ generated ylides
Parmar, Sangeeta,Pawar, Sharad P.,Iyer, Ramkumar,Kalia, Dimpy
supporting information, p. 14926 - 14929 (2019/12/24)
A technically simple approach for rapid, high-yielding and site-selective bioconjugation has been developed for both in vitro and cellular applications. This method involves the generation of maleimido-phosphonium ylides via 4-nitrophenol catalysis under physiological conditions followed by their Wittig reactions with aldehyde-appended biomolecules.
The versatility of N-alkyl-methoxyamine bi-functional linkers for the preparation of glycoconjugates
Munneke, Stefan,Dangerfield, Emma M.,Stocker, Bridget L.,Timmer, Mattie S. M.
, p. 633 - 642 (2017/09/18)
The application of N-glycosyl-N-alkyl-methoxyamine bi-functional linkers for the synthesis of a variety of glycoconjugates is described. The linker contains a specific functional group, such as an amine, azide, thiol, or carboxylic acid, which can be used for conjugation methodologies that include amide ligation, sulfonylation, copper-mediated Huisgen cycloaddition or thiol-maleimide coupling. In this way, glycoconjugates equipped with biotin, a fluorescent reporter, or a protein were efficiently synthesised, thus demonstrating the versatility of this type of oxyamine linker for the construction of glycoconjugate probes.
Stable and Rapid Thiol Bioconjugation by Light-Triggered Thiomaleimide Ring Hydrolysis
Kalia, Dimpy,Pawar, Sharad P.,Thopate, Jyoti S.
supporting information, p. 1885 - 1889 (2017/02/05)
Maleimide-mediated thiol-specific derivatization of biomolecules is one of the most efficacious bioconjugation approaches currently available. Alarmingly, however, recent work demonstrates that the resulting thiomaleimide conjugates are susceptible to breakdown via thiol exchange reactions. Herein, we report a new class of maleimides, namely o-CH2NHiPr phenyl maleimides, that undergo unprecedentedly rapid ring hydrolysis after thiol conjugation to form stable thiol exchange-resistant conjugates. Furthermore, we overcome the problem of low shelf lives of maleimide reagents owing to their propensity to undergo ring hydrolysis prior to bioconjugation by developing a photocaged version of this scaffold that resists ring hydrolysis. UV irradiation of thiol bioconjugates formed with this photocaged maleimide unleashes rapid thiomaleimide ring hydrolysis to yield the desired stable conjugates within 1 h under gentle, ice-cold conditions.
One-pot: N -glycosylation remodeling of IgG with non-natural sialylglycopeptides enables glycosite-specific and dual-payload antibody-drug conjugates
Tang, Feng,Yang, Yang,Tang, Yubo,Tang, Shuai,Yang, Liyun,Sun, Bingyang,Jiang, Bofeng,Dong, Jinhua,Liu, Hong,Huang, Min,Geng, Mei-Yu,Huang, Wei
supporting information, p. 9501 - 9518 (2016/10/22)
Chemoenzymatic transglycosylation catalyzed by endo-S mutants is a powerful tool for in vitro glycoengineering of therapeutic antibodies. In this paper, we report a one-pot chemoenzymatic synthesis of glycoengineered Herceptin using an egg-yolk sialylglycopeptide (SGP) substrate. Combining this one-pot strategy with novel non-natural SGP derivatives carrying azido or alkyne tags, glycosite-specific conjugation was enabled for the development of new antibody-drug conjugates (ADCs). The site-specific ADCs and semi-site-specific dual-drug ADCs were successfully achieved and characterized with SDS-PAGE, intact antibody or ADC mass spectrometry analysis, and PNGase-F digestion analysis. Cancer cell cytotoxicity assay revealed that small-molecule drug release of these ADCs relied on the cleavable Val-Cit linker fragment embedded in the structure. These results represent a new approach for glycosite-specific and dual-drug ADC design and rapid synthesis, and also provide the structural requirement for their biologic activities.
Thiol-reactive Fluorescent probes for Protein Labelling
Corrie, John E. T.
, p. 2975 - 2982 (2007/10/02)
Cyclisation of N-alkylmaleic acids mediated by acetic anhydride in dimethylacetamide in the presence of traces of cobalt naphthenate has been used for efficient assembly of a range of fluorescent maleimide reagents.The fluorescence responses of these reagents to addition of thiol across the maleimide double bond, and to hydrolysis of the meleimide ring, are described.
