Preparation of Protein Conjugates via Homobifunctional Diselenoester Cross-Linker

Yin, Xuguang; Gao, Xiang; Du, Jingjing; Zhang, Xiaokang; Chen, Xiang-Zhao; Wang, Jian; Xin, Ling-Ming; Lei, Ze; Liu, Zheng; Guo, Jun

doi:10.1021/acs.orglett.6b02568

Cited by 14 publications

(7 citation statements)

References 44 publications

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“…36 According to our previous study on protein conjugation, the selenoester displays better combination of stability and reactivity than the commonly used active esters (N-hydroxysuccinimide, p-nitrophenyl, and polyfluorophenyl esters). 36,37 The incorporation number per BSA molecule is 18, which was determined by the MALDI-TOF mass spectrometry. Compound 11 was applied as the coating antigen for ELISA of antinicotine antibodies (Scheme 2c).…”

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confidence: 99%

Peptide-free Synthetic Nicotine Vaccine Candidates with α-Galactosylceramide as Adjuvant

et al. 2019

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Peptides are generally needed as T-helper epitopes in nicotine vaccines to induce effective antibody responses, but the highly polymorphic property of major histocompatibility complex (MHC) molecules may limit opportunities of B cell to receive CD4+ T-cell help. Invariant natural killer T (iNKT) cells recognize lipid antigens presented by the nonpolymorphic CD1d molecule that is conserved in mammals to a great extent. iNKT cells also display some similar functions to conventional CD4+ T-helper cells, especially they license dendritic cells stimulate antibody isotype switching by B cells. Herein, α-galactosylceramide (αGalCer), a classical iNKT cell agonist, serves as an adjuvant in synthetic nicotine vaccine candidates absent of peptide or protein. Our study reveals that αGalCer displays better adjuvant activity than Pam3CSK4 (a commonly used lipopeptide TLR agonist). Remarkably, the covalent linker between the nicotine hapten and αGalCer is not critical. Self-assembly of the lipid-tailed nicotine and αGalCer into the liposome represents a structurally simple but immunologically effective way to develop nicotine vaccines. This is the first time to introduce the iNKT cell agonist as an adjuvant to an antidrug vaccine. This discovery may contribute to improving the efficacy of clinical candidate nicotine vaccines in the future.

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confidence: 99%

Peptide-free Synthetic Nicotine Vaccine Candidates with α-Galactosylceramide as Adjuvant

et al. 2019

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“…We initially tested the ligation of these selenopeptide dimers with peptide thioesters; however, the rates of the ligation reactions were extremely slow (see the SI for details). Therefore, we focused on ligations using the peptide selenoesters. ,, …”

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Development of Powerful Auxiliary-Mediated Ligation To Facilitate Rapid Protein Assembly

et al. 2019

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Here, we describe an Se-auxiliary mediated ligation protocol capable of rapid native chemical ligations at sterically hindered junctions, followed by in situ auxiliary cleavage under neutral conditions without affecting unprotected Cys residues. This auxiliary, which is prepared from phenyl acetaldehyde in one step, can be conveniently attached to the N-terminal region of a peptide via a reductive amination or coupling reaction. We demonstrated this methodology by synthesizing two protein samples.

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“…The preparation of STn-αGalCer ( 1 ) (shown in Scheme A) began with hydrogenolysis of azide 3 by H 2 in the presence of Pd/C followed by amidation of the resulting amine via an adipic acid p -nitrophenyl diester ( 4 ). The activated ester 5 was then subjected to the coupling with 6α (see the synthesis of 6α and 6β in the Supporting Information) to afford the protected STn-αGalCer conjugate 7 .…”

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confidence: 99%

“…When a hapten/protein ratio of 30:1 was employed, the average number of STn hapten loaded per BSA was 11.6. It is noteworthy that under same conditions the use of linker 4 led to a lower loading level of STn hapten (4 STn per BSA) …”

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IgG Antibody Response Elicited by a Fully Synthetic Two-Component Carbohydrate-Based Cancer Vaccine Candidate with α-Galactosylceramide as Built-in Adjuvant

et al. 2017

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A fully synthetic self-adjuvanting cancer vaccine candidate was constructed through covalent conjugation of invariant natural killer T (iNKT) cell ligand α-galactosylceramide (αGalCer) with sialyl Tn (STn), a representative tumor-associated carbohydrate antigen (TACA). This two-component vaccine STn-αGalCer is devoid of antigenic peptide, featuring the well-defined structure with high simplicity. STn-αGalCer showed remarkable efficacy in inducing antibody class switching from IgM to STn-specific IgG. Subtypes of IgG antibody were primarily IgG1 and IgG3.

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Preparation of Protein Conjugates via Homobifunctional Diselenoester Cross-Linker

Cited by 14 publications

References 44 publications

Peptide-free Synthetic Nicotine Vaccine Candidates with α-Galactosylceramide as Adjuvant

Peptide-free Synthetic Nicotine Vaccine Candidates with α-Galactosylceramide as Adjuvant

Development of Powerful Auxiliary-Mediated Ligation To Facilitate Rapid Protein Assembly

IgG Antibody Response Elicited by a Fully Synthetic Two-Component Carbohydrate-Based Cancer Vaccine Candidate with α-Galactosylceramide as Built-in Adjuvant

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