Site-selective chemical methods for protein bioconjugation have revolutionized the fields of cell and chemical biology through the development of novel protein/enzyme probes bearing fluorescent, spectroscopic, or even toxic cargos. Herein, we report two new methods for the bioconjugation of α-oxo aldehyde handles within proteins using small molecule aniline and/or phenol probes. The "α-oxo-Mannich" and "catalyst-free aldol" ligations both compete for the electrophilic α-oxo aldehyde, which displays pH divergent reactivity proceeding through the "Mannich" pathway at acidic pH to afford bifunctionalized bioconjugates, and the "catalyst-free aldol" pathway at neutral pH to afford monofunctionalized bioconjugates. We explore the substrate scope and utility of both of these bioconjugations in the construction of neoglycoproteins, in the process formulating a mechanistic rationale for how both pathways intersect with each other at different reaction pH's.
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http://dx.doi.org/10.1021/acschembio.1c00531 | DOI Listing |
Zool Res
January 2025
Institute of Preventive Medicine, School of Public Health, Dali University, Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan, Yunnan Key Laboratory of Zoonotic Disease Cross-border Prevention and Quarantine, Dali, Yunnan 671000, China. E-mail:
The family has seen an explosive expansion in its host range in recent years, yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown. The emergence of rat hepatitis E virus (HEV) has introduced a new public health threat due to its potential for zoonotic transmission. This study investigated 2 464 wild small mammals spanning four animal orders, eight families, 21 genera, and 37 species in Yunnan Province, China.
View Article and Find Full Text PDFNat Commun
January 2025
College of Chemistry and Life Science, Advanced Institute of Materials Science, Changchun University of Technology, Changchun, P. R. China.
The enantioselective domino Heck/cross-coupling has emerged as a powerful tool in modern chemical synthesis for decades. Despite significant progress in relative rigid skeleton substrates, the implementation of asymmetric Heck/cross-coupling cascades of highly flexible haloalkene substrates remains a challenging and and long-standing goal. Here we report an efficient asymmetric domino Heck/Tsuji-Trost reaction of highly flexible vinylic halides with 1,3-dienes enabled by palladium catalysis.
View Article and Find Full Text PDFHorm Behav
January 2025
Department of Integrative Biology, University of Texas at Austin, Austin, TX 78712, United States of America. Electronic address:
Individual variation in stress coping styles is widespread and consequential to health and fitness. Proactive (bold behavior, low stress reactivity, low cognitive flexibility) and reactive (shy behavior, high stress reactivity, high cognitive flexibility) coping styles are found in many species, but the developmental forces shaping them remain elusive. We examined how social influences, specifically mating interactions, shape the development of adult female coping styles with a manipulative rearing experiment using El Abra swordtails, Xiphophorus nigrensis.
View Article and Find Full Text PDFChemistry
January 2025
University of Oxford, Inorganic Chemistry Laboratory, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.
Combining experiment and theory, the mechanisms of H2 activation by the potassium-bridged aluminyl dimer K2[Al(NON)]2 (NON = 4,5-bis(2,6-diisopropylanilido)-2,7-di-tertbutyl-9,9-dimethylxanthene) and its monomeric K+-sequestered counterpart have been investigated. These systems show diverging reactivity towards the activation of dihydrogen, with the dimeric species undergoing formal oxidative addition of H2 at each Al centre under ambient conditions, and the monomer proving to be inert to dihydrogen addition. Noting that this K+ dependence is inconsistent with classical models of single-centre reactivity for carbene-like Al(I) species, we rationalize these observations instead by a cooperative frustrated Lewis pair (FLP)-type mechanism (for the dimer) in which the aluminium centre acts as the Lewis base and the K+ centres as Lewis acids.
View Article and Find Full Text PDFJ Clin Immunol
January 2025
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study.
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