Defect-engineered carbon materials have been emerged as promising electrocatalysts for oxygen reduction reaction(ORR)in metal-air batteries.Developing a facile strategy for the preparation of highly active nanocarbon ...Defect-engineered carbon materials have been emerged as promising electrocatalysts for oxygen reduction reaction(ORR)in metal-air batteries.Developing a facile strategy for the preparation of highly active nanocarbon electrocatalysts remains challenging.Herein,a low-cost and simple route is developed to synthesize defective graphene by pyrolyzing the mixture of glucose and carbon nitride.Molecular dynamics simulations reveal that the graphene formation is ascribed to two-dimensional layered feature of carbon nitride,and high compatibility of carbon nitride/glucose systems.Structural measurements suggest that the graphene possesses rich edge and topological defects.The graphene catalyst exhibits higher power density than commercial Pt/C catalyst in a primary Zn-air battery.Combining experimental results and theoretical thermodynamic analysis,it is identified that graphitic nitrogen-modified topological defects at carbon framework edges are responsible for the decent ORR performance.The strategy presented in this work can be can be scaled up readily to fabricate defective carbon materials.展开更多
A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The l...A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The linear decapeptide was assembled by standard Boc chemistry on solid-phase and subsequently cyclized in solution with high efficiency and reproducibility. In subsequent purification by semi-preparative HPLC,50%(v/v) DMF/H_2O was employed as the solvent to overcome the difficulty of solubilizat...展开更多
Proton NMR-spectra of Wang resin bound compounds were obtained using the magic angle spinning 1HNMR technique with standard equipment. It was possible to analyse the spectra to evaluate their utility in solid-phase ch...Proton NMR-spectra of Wang resin bound compounds were obtained using the magic angle spinning 1HNMR technique with standard equipment. It was possible to analyse the spectra to evaluate their utility in solid-phase chernistry. A typical example was presented, which could directly monitor solid-phase展开更多
Automated chemical solid-phase synthesis is an automation platform for rapid and reliable synthesis of glycans.Since the seminal work of Automated Glycan Assembly(AGA)disclosed by Seeberger in 2001,AGA has evolved fro...Automated chemical solid-phase synthesis is an automation platform for rapid and reliable synthesis of glycans.Since the seminal work of Automated Glycan Assembly(AGA)disclosed by Seeberger in 2001,AGA has evolved from a proof-of-concept to a robust and reliable technology for streamlined production of various types of glycans.Through more than 20 years of unceasing efforts,the major breakthroughs in AGA including linkers,approved building blocks,and synthesizers have been acquired,and numerous influential achievements have been made in complex glycan synthesis.In addition,the HPLC-assisted automated synthesis emerges as a promising automation platform to access glycans.In this review,we highlight the key advances in the field of automated chemical solid-phase synthesis,especially in AGA.The synthesis of representative glycans based on AGA is also described.展开更多
A new conformationally restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our 揗eshed-Bag Gathered-Bunch?method with a combination of Fmoc, allyl and N-1-(4,4-dimethyl2,6-dioxocyc...A new conformationally restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our 揗eshed-Bag Gathered-Bunch?method with a combination of Fmoc, allyl and N-1-(4,4-dimethyl2,6-dioxocyclo-hexylidene)ethyl chemical protection strategy.展开更多
The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and versatility.Chemi...The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and versatility.Chemical protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image proteins.This review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic methods.Furthermore,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse proteins.Recent applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further discussed.Together,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis.展开更多
The combination of hydrophobic polymers with nucleic acids is a fascinating way to engineer the self-assembly behavior of nucleic acids into diverse nanostructures such as micelles,vesicles,nanosheets,and worms.Here w...The combination of hydrophobic polymers with nucleic acids is a fascinating way to engineer the self-assembly behavior of nucleic acids into diverse nanostructures such as micelles,vesicles,nanosheets,and worms.Here we developed a robust route to synthesize a RNA macroinitiator with protecting groups on the 2′-hydroxyl groups in the solid phase using an oligonucleotide synthesizer.The protecting groups successfully solubilized the RNA macroinitiator,enabling atom transfer radical polymerization(ATRP)of hydrophobic monomers.As a result,the RNA−polymer hybrids obtained by ATRP exhibited enhanced chemical stability by suppressing cleavage.In addition,we demonstrated evidence of controlled polymerization behavior as well as control over the molecular weight of the hydrophobic polymers grown from RNA.We envision that this methodology will expand the field of RNA−polymer conjugates while vastly enhancing the possibility to alter and engineer the properties of RNA-based polymeric materials.展开更多
Chemical synthesis of proteins containing up to 300 amino acids may cover 30%—50%of all the proteins encountered in biomedical studies and may provide an alternate approach to the usually used recombinant expression ...Chemical synthesis of proteins containing up to 300 amino acids may cover 30%—50%of all the proteins encountered in biomedical studies and may provide an alternate approach to the usually used recombinant expression teclmology,vastly expanding the chemical space of the latter.In the present review article,we tried to survey the recent progresses made for more rapid synthesis of increasingly long peptides and more efficient ligation of multiple peptide segments.The developments of seminal methods by many research groups have greatly contributed to the recent breakthroughs in the successful total synthesis of a number of functionally important proteins,such as oligoubiquitins,bacterial GroEL/ES chaperones,and mirror-image DNA polymerases.Through these studies,a potential bottleneck has also been recognized for the chemical synthesis of large proteins,namely,how to ensure that each peptide segment from a large protein avoids unfavorable aggregation when dissolved in aqueous solution.Many new methods,such as removable backbone modification(RBM)strategy have been developed to overcome this bottleneck,while more studies need to be carried out to develop more effective and less costly methods that ultimately,may lead to fully automatable chemical synthesis of customized proteins of 300 amino acids bearing any artificial designs.展开更多
The synthesis of an Asp lactam derivative of A-183,a selective inhibitor of Factor 7a with good anticoagulant and antithrombotic activity,is described.Our synthesis depends on the use of a removable backbone modificat...The synthesis of an Asp lactam derivative of A-183,a selective inhibitor of Factor 7a with good anticoagulant and antithrombotic activity,is described.Our synthesis depends on the use of a removable backbone modification(RBM)strategy to prevent aspartimide formation,which thwarted all attempts to synthesize this target using direct solid-phase peptide synthesis.Validation of the RBM strategy in the synthesis of a second Asp lactam derivative was also accomplished.The RBM strategy is therefore proposed as a general method for the synthesis of Asp lactam cyclic peptides.展开更多
[Objectives]This study was conducted to synthesize sea anemone peptide toxin Ap-TxI and investigate its insecticidal activity. [Methods] The sea anemone linear peptide toxin Ap-TxI was synthesized by the solid-phase p...[Objectives]This study was conducted to synthesize sea anemone peptide toxin Ap-TxI and investigate its insecticidal activity. [Methods] The sea anemone linear peptide toxin Ap-TxI was synthesized by the solid-phase peptide synthesis(SPPS), and six cysteines were oxidized to form three disulfide bonds by a three-step directional oxidation method. Then, purification by high performance liquid chromatography(HPLC) and mass spectrometry identification were performed. Finally, the insect cytotoxicity and insecticidal activity of Ap-TxI were studied by the MTT method and insect injection method. [Results] The oxidized peptide Ap-TxI with three disulfide bonds in natural configuration was successfully synthesized by the SPPS method, and its purity was >90% by HPLC analysis. The results of the MTT method showed that Ap-TxI was active on the growth of insect cells sf9, with a half effective dose of 0.2 nM;and the results of the mealworm injection test showed that the polypeptide Ap-TxI had high insecticidal activity with a median lethal dose of 11.7 nM. [Conclusions] The sea anemone peptide toxin Ap-TxI with high insecticidal effect was obtained, laying a foundation for the development of new, efficient and safe biological insecticides.展开更多
TNFR1-associated death domain protein(TRADD)with arginine N-GlcNAcylation is a novel and structurally unique posttranslational modification(PTM)glycoprotein that blocks the formation of death-inducing signaling comple...TNFR1-associated death domain protein(TRADD)with arginine N-GlcNAcylation is a novel and structurally unique posttranslational modification(PTM)glycoprotein that blocks the formation of death-inducing signaling complex(DISC),orchestrating host nuclear factorκB(NF-κB)signaling in entero-pathogenic Escherichia coli(EPEC)-infected cells.This particular glycosylated modification plays an extremely vital role for the effective colonization and pathogenesis of pathogens in the gut.Herein we describe the total synthesis of TRADD death domain(residues 195-312)with arginine235 NGlcNAcylation(Arg-GIcNAc TRADD(195-312)).Two longish peptidyl fragments of the wild-type primary sequence were obtained by robust,microwave-assisted,highly efficient,solid-phase peptide synthesis(SPPS),the N-GlcNAcylated sector was built by total synthesis and attached specifically to resinbound peptide with an unprotected ornithine residue via silver-promoted on-resin guanidinylation,ArgGlcNAc TRADD(195-312)was constructed by hydrazide-based native chemical ligation(NCL).The facile synthetic strategy is expected to be generally applicable for the rapid synthesis of other proteins with Arg-GIcNAc modification and to pave the way for the related chemically biological study.展开更多
单晶型高镍三元层状氧化物凭借高能量密度、长循环寿命和优异的安全性成为新一代锂离子电池理想的正极材料.目前,单晶型高镍三元正极通过“共沉淀+高温锂化”两步制备,不仅工艺繁琐、原材料选择单一,制备过程还会产生大量废水/气.本文...单晶型高镍三元层状氧化物凭借高能量密度、长循环寿命和优异的安全性成为新一代锂离子电池理想的正极材料.目前,单晶型高镍三元正极通过“共沉淀+高温锂化”两步制备,不仅工艺繁琐、原材料选择单一,制备过程还会产生大量废水/气.本文提出了一种新的全干法固相合成策略,实现了单晶型高镍三元正极低成本、无废水绿色制备.在煅烧过程引入锶/钛离子作为烧结助剂,降低烧结温度来缓解锂/氧流失,从而降低锂镍混排并稳定晶格氧.此外,针对固相合成过程锂化动力学缓慢导致表面残碱较高的问题,引入硼化合物与残碱反应,不仅有效提升了界面稳定性,而且形成的离子导体还能够加速锂离子在界面处的迁移.因此,制备的单晶型高镍三元正极在0.1 C电流密度下比容量可达到191.1 mA h g^(-1),以1 C电流密度在软包全电池中循环500次后仍具有90.1%的容量保持率.展开更多
Sequence-defined oligocarbamates were synthesized by orthogonal iterative chemistry on a modified Wang solid support.In this approach,amino alcohol building blocks,containing either primary or secondary amines,were us...Sequence-defined oligocarbamates were synthesized by orthogonal iterative chemistry on a modified Wang solid support.In this approach,amino alcohol building blocks,containing either primary or secondary amines,were used in order to obtain ondemand either a classical urethane motif−NH−CO−O−or a Nsubstituted urethane linkage−NR−CO−O−.Hence,aperiodic carbamate sequences could be easily prepared in this work.Polymers with different monomer sequences and chain-length were synthesized.Characterization by NMR,SEC and ESI-MS indicated formation of near-monodisperse polymers.Furthermore,these informational oligocarbamates were sequenced by MS/MS.Very interestingly,it was found that a fully orthogonal fragmentation of−NH−CO−O−urethane motifs occurs in these macromolecules.展开更多
Peptides can be potentmolecules with high efficacy and selectivity in the development of biotherapeutics.However,the poor pharmacokinetic properties of peptides pose major challenges for their broader medicinal applic...Peptides can be potentmolecules with high efficacy and selectivity in the development of biotherapeutics.However,the poor pharmacokinetic properties of peptides pose major challenges for their broader medicinal applications.Inspired by the proteinstabilizing role of natural N-glycosylation,we design and synthesize a series of parathyroid hormone(PTH)peptides(1-34),bearing either N-GlcNAc or biantennary complex-type N-glycan modification,and evaluate their serum stability and biological activities.The results indicate that an N-Asn-linked complex-type sialylundecasaccharide can increase the serum half-life and in vivo bioactivity of PTH peptides with a broad tolerance of modification sites.Further,hydrogen/deuterium exchange mass spectroscopy indicates that the larger-sized Nglycan can induce enhanced hydration dynamics in its surroundings,which may facilitate an improved resistance for the peptide against enzymatic proteolysis.This sialylundecasaccharide-based peptideengineering strategy has also been applied to glucagon-like peptide-1(7-37),leading to glycopeptides with enhanced hypoglycemic activity and acting time in vivo.Together,these results demonstrate the potential of using sialylated complextype N-glycan as a general engineering strategy for developing long-acting peptide therapeutics.展开更多
HYL derived from the venom of the solitary bee Hylaeus signatus(Hymenoptera:Colletidae)is anα-helical antimicrobial peptide with 16 residues.To explore whether HYL can be applied in anti-tumor therapy,we synthesized ...HYL derived from the venom of the solitary bee Hylaeus signatus(Hymenoptera:Colletidae)is anα-helical antimicrobial peptide with 16 residues.To explore whether HYL can be applied in anti-tumor therapy,we synthesized HYL and further modified its structure by using a solid-phase synthesis method,and then evaluated their antitumor activities.Firstly,we identified the key residues of HYL by alanine scanning strategy,and then a series of stapled peptides were synthesized by hydrocarbon stapling strategy without destroying the key residues.All the stapled peptides of HYL showed significant improvement not only inα-helicity,but also in antitumor activity and protease resistance when compared to the parent peptide HYL.The results showed that hydrophobicity and amphiphilicity are important factors affecting the antitumor activity of HYL,and the stapling strategy can significantly affect the proteolytic stability and helicity of HYL.What’s more,we find that the stapled peptides HYL-14,HYL-16 and HYL-18 show a promising prospect for novel anti-tumor drug development.展开更多
Hainantoxin-Ⅳ(HNTX-Ⅳ)was isolated from the Chinese bird spider Ornithoctorcs hainana and identified as a novel antagonist of tetrodotoxin-sensitive(TTX-S)sodium channels.As revealed by the solution structure of HNTX...Hainantoxin-Ⅳ(HNTX-Ⅳ)was isolated from the Chinese bird spider Ornithoctorcs hainana and identified as a novel antagonist of tetrodotoxin-sensitive(TTX-S)sodium channels.As revealed by the solution structure of HNTX-Ⅳ solved by two-dimensional nuclear magnetic resonance(2D-NMR),HNTX-Ⅳ adopts an inhibitor cystine knot motif.To check the role of basic residues during HNTX-Ⅳ’s interaction with TTX-S sodium channels,R26A and K27A mutants of HNTX-Ⅳ were constructed by solid-phase chemical synthesis.The synthesized peptides were purified and refolded under optimized oxidation conditions.Correct synthesis and folding were confirmed by MALDI-TOF mass spectrometry and NMR spectroscopy,respectively.Using the whole-cell patch-clamp technique,Lys27 but not Arg26 was identified as a key residue for HNTX-Ⅳ’s bioactivity against TTX-S sodium channels,because R26A-HNTX-Ⅳ showed slightly reduced activity and K27A-HNTX-Ⅳ showed almost no inhibition.展开更多
基金supported by the National Natural Science Foundation of China(21838003,91834301 and 21978278)the Shanghai Scientific and Technological Innovation Project(18JC1410500 and 19JC1410400)the Fundamental Research Funds for the Central Universities(222201718002).
文摘Defect-engineered carbon materials have been emerged as promising electrocatalysts for oxygen reduction reaction(ORR)in metal-air batteries.Developing a facile strategy for the preparation of highly active nanocarbon electrocatalysts remains challenging.Herein,a low-cost and simple route is developed to synthesize defective graphene by pyrolyzing the mixture of glucose and carbon nitride.Molecular dynamics simulations reveal that the graphene formation is ascribed to two-dimensional layered feature of carbon nitride,and high compatibility of carbon nitride/glucose systems.Structural measurements suggest that the graphene possesses rich edge and topological defects.The graphene catalyst exhibits higher power density than commercial Pt/C catalyst in a primary Zn-air battery.Combining experimental results and theoretical thermodynamic analysis,it is identified that graphitic nitrogen-modified topological defects at carbon framework edges are responsible for the decent ORR performance.The strategy presented in this work can be can be scaled up readily to fabricate defective carbon materials.
基金supported by National Natural Science Foundation(No.30672546)Shanghai Municipal Committee of S & T(No.0652nm013)National Key Basic Research Program of China(No.2007CB935800)
文摘A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The linear decapeptide was assembled by standard Boc chemistry on solid-phase and subsequently cyclized in solution with high efficiency and reproducibility. In subsequent purification by semi-preparative HPLC,50%(v/v) DMF/H_2O was employed as the solvent to overcome the difficulty of solubilizat...
文摘Proton NMR-spectra of Wang resin bound compounds were obtained using the magic angle spinning 1HNMR technique with standard equipment. It was possible to analyse the spectra to evaluate their utility in solid-phase chernistry. A typical example was presented, which could directly monitor solid-phase
文摘Automated chemical solid-phase synthesis is an automation platform for rapid and reliable synthesis of glycans.Since the seminal work of Automated Glycan Assembly(AGA)disclosed by Seeberger in 2001,AGA has evolved from a proof-of-concept to a robust and reliable technology for streamlined production of various types of glycans.Through more than 20 years of unceasing efforts,the major breakthroughs in AGA including linkers,approved building blocks,and synthesizers have been acquired,and numerous influential achievements have been made in complex glycan synthesis.In addition,the HPLC-assisted automated synthesis emerges as a promising automation platform to access glycans.In this review,we highlight the key advances in the field of automated chemical solid-phase synthesis,especially in AGA.The synthesis of representative glycans based on AGA is also described.
文摘A new conformationally restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our 揗eshed-Bag Gathered-Bunch?method with a combination of Fmoc, allyl and N-1-(4,4-dimethyl2,6-dioxocyclo-hexylidene)ethyl chemical protection strategy.
基金supported by the National Key R&D Program of China(2022YFC3401500)the National Natural Science Foundation of China(22137005,92253302,22227810 to Lei Liu,22177004,92153301,22321005 to Suwei Dong,22277020 to Yiming Li,22022703,22177108,22377118 to Ji-Shen Zheng,92353302,22177059 to Yongxiang Chen,22177035 to Jun Guo,22277029,22077036 to Chunmao He,22077078 to Honggang Hu92353302,92053108 to Yanmei Li,22277015 to Junfeng Zhao)。
文摘The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and versatility.Chemical protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image proteins.This review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic methods.Furthermore,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse proteins.Recent applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further discussed.Together,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis.
基金NSF DMR 2202747 and DTRA grant HDTRA1-20-1-0014.G.S.gratefully acknowledges the Polish National Agency for Academic Exchange(BPN/PPO/2022/1/00027)for financial support。
文摘The combination of hydrophobic polymers with nucleic acids is a fascinating way to engineer the self-assembly behavior of nucleic acids into diverse nanostructures such as micelles,vesicles,nanosheets,and worms.Here we developed a robust route to synthesize a RNA macroinitiator with protecting groups on the 2′-hydroxyl groups in the solid phase using an oligonucleotide synthesizer.The protecting groups successfully solubilized the RNA macroinitiator,enabling atom transfer radical polymerization(ATRP)of hydrophobic monomers.As a result,the RNA−polymer hybrids obtained by ATRP exhibited enhanced chemical stability by suppressing cleavage.In addition,we demonstrated evidence of controlled polymerization behavior as well as control over the molecular weight of the hydrophobic polymers grown from RNA.We envision that this methodology will expand the field of RNA−polymer conjugates while vastly enhancing the possibility to alter and engineer the properties of RNA-based polymeric materials.
基金Supported by the National Key R&D Program of China(No.2017YFA0505200)the National Natural Science Foundation of China(Nos.21532004,91753205,81621002).
文摘Chemical synthesis of proteins containing up to 300 amino acids may cover 30%—50%of all the proteins encountered in biomedical studies and may provide an alternate approach to the usually used recombinant expression teclmology,vastly expanding the chemical space of the latter.In the present review article,we tried to survey the recent progresses made for more rapid synthesis of increasingly long peptides and more efficient ligation of multiple peptide segments.The developments of seminal methods by many research groups have greatly contributed to the recent breakthroughs in the successful total synthesis of a number of functionally important proteins,such as oligoubiquitins,bacterial GroEL/ES chaperones,and mirror-image DNA polymerases.Through these studies,a potential bottleneck has also been recognized for the chemical synthesis of large proteins,namely,how to ensure that each peptide segment from a large protein avoids unfavorable aggregation when dissolved in aqueous solution.Many new methods,such as removable backbone modification(RBM)strategy have been developed to overcome this bottleneck,while more studies need to be carried out to develop more effective and less costly methods that ultimately,may lead to fully automatable chemical synthesis of customized proteins of 300 amino acids bearing any artificial designs.
基金supported by the National Key R&D Program of China(No.2017YFA0505200)the National Natural Science Foundation of China(Nos.91753205,21877024,21621003,81621002)the Fundamental Research Funds for the Central Universities(No.JZ2019HGPB0105).
文摘The synthesis of an Asp lactam derivative of A-183,a selective inhibitor of Factor 7a with good anticoagulant and antithrombotic activity,is described.Our synthesis depends on the use of a removable backbone modification(RBM)strategy to prevent aspartimide formation,which thwarted all attempts to synthesize this target using direct solid-phase peptide synthesis.Validation of the RBM strategy in the synthesis of a second Asp lactam derivative was also accomplished.The RBM strategy is therefore proposed as a general method for the synthesis of Asp lactam cyclic peptides.
基金Supported by Natural Science Foundation of Hainan Province (820RC636)Undergraduate Innovation and Enterpreneurship Training Program of Hainan Province (X202011810003)Special Fund for Academician Innovation Platform in Hainan Province (YSPTZX202132)。
文摘[Objectives]This study was conducted to synthesize sea anemone peptide toxin Ap-TxI and investigate its insecticidal activity. [Methods] The sea anemone linear peptide toxin Ap-TxI was synthesized by the solid-phase peptide synthesis(SPPS), and six cysteines were oxidized to form three disulfide bonds by a three-step directional oxidation method. Then, purification by high performance liquid chromatography(HPLC) and mass spectrometry identification were performed. Finally, the insect cytotoxicity and insecticidal activity of Ap-TxI were studied by the MTT method and insect injection method. [Results] The oxidized peptide Ap-TxI with three disulfide bonds in natural configuration was successfully synthesized by the SPPS method, and its purity was >90% by HPLC analysis. The results of the MTT method showed that Ap-TxI was active on the growth of insect cells sf9, with a half effective dose of 0.2 nM;and the results of the mealworm injection test showed that the polypeptide Ap-TxI had high insecticidal activity with a median lethal dose of 11.7 nM. [Conclusions] The sea anemone peptide toxin Ap-TxI with high insecticidal effect was obtained, laying a foundation for the development of new, efficient and safe biological insecticides.
基金the National Natural Science Foundation of China (Nos.91849129,21807112)PLA Youth Medical Science and Technology Youth Development Program (No.16QNP086)Foundation of Second Military Medical University (No.2016JS11)
文摘TNFR1-associated death domain protein(TRADD)with arginine N-GlcNAcylation is a novel and structurally unique posttranslational modification(PTM)glycoprotein that blocks the formation of death-inducing signaling complex(DISC),orchestrating host nuclear factorκB(NF-κB)signaling in entero-pathogenic Escherichia coli(EPEC)-infected cells.This particular glycosylated modification plays an extremely vital role for the effective colonization and pathogenesis of pathogens in the gut.Herein we describe the total synthesis of TRADD death domain(residues 195-312)with arginine235 NGlcNAcylation(Arg-GIcNAc TRADD(195-312)).Two longish peptidyl fragments of the wild-type primary sequence were obtained by robust,microwave-assisted,highly efficient,solid-phase peptide synthesis(SPPS),the N-GlcNAcylated sector was built by total synthesis and attached specifically to resinbound peptide with an unprotected ornithine residue via silver-promoted on-resin guanidinylation,ArgGlcNAc TRADD(195-312)was constructed by hydrazide-based native chemical ligation(NCL).The facile synthetic strategy is expected to be generally applicable for the rapid synthesis of other proteins with Arg-GIcNAc modification and to pave the way for the related chemically biological study.
基金supported by the National Natural Science Foundation of China(U22A20429,22308103)China Postdoctoral Science Foundation(2023M731083)the Fundamental Research Funds for the Central Universities。
文摘单晶型高镍三元层状氧化物凭借高能量密度、长循环寿命和优异的安全性成为新一代锂离子电池理想的正极材料.目前,单晶型高镍三元正极通过“共沉淀+高温锂化”两步制备,不仅工艺繁琐、原材料选择单一,制备过程还会产生大量废水/气.本文提出了一种新的全干法固相合成策略,实现了单晶型高镍三元正极低成本、无废水绿色制备.在煅烧过程引入锶/钛离子作为烧结助剂,降低烧结温度来缓解锂/氧流失,从而降低锂镍混排并稳定晶格氧.此外,针对固相合成过程锂化动力学缓慢导致表面残碱较高的问题,引入硼化合物与残碱反应,不仅有效提升了界面稳定性,而且形成的离子导体还能够加速锂离子在界面处的迁移.因此,制备的单晶型高镍三元正极在0.1 C电流密度下比容量可达到191.1 mA h g^(-1),以1 C电流密度在软包全电池中循环500次后仍具有90.1%的容量保持率.
基金the CSC Graduate School funded by the French National Research Agency(CSC-IGS ANR-17-EURE-0016)for a PhD fellowship.
文摘Sequence-defined oligocarbamates were synthesized by orthogonal iterative chemistry on a modified Wang solid support.In this approach,amino alcohol building blocks,containing either primary or secondary amines,were used in order to obtain ondemand either a classical urethane motif−NH−CO−O−or a Nsubstituted urethane linkage−NR−CO−O−.Hence,aperiodic carbamate sequences could be easily prepared in this work.Polymers with different monomer sequences and chain-length were synthesized.Characterization by NMR,SEC and ESI-MS indicated formation of near-monodisperse polymers.Furthermore,these informational oligocarbamates were sequenced by MS/MS.Very interestingly,it was found that a fully orthogonal fragmentation of−NH−CO−O−urethane motifs occurs in these macromolecules.
基金This research was made possible as a result of a generous grant from the Beijing National Science Foundation(grant no.JQ18024)the National Key R&D Program of China(grant no.2018YFA0507602)the National Natural Science Foundation of China(grant nos.91953111 and 91853113).
文摘Peptides can be potentmolecules with high efficacy and selectivity in the development of biotherapeutics.However,the poor pharmacokinetic properties of peptides pose major challenges for their broader medicinal applications.Inspired by the proteinstabilizing role of natural N-glycosylation,we design and synthesize a series of parathyroid hormone(PTH)peptides(1-34),bearing either N-GlcNAc or biantennary complex-type N-glycan modification,and evaluate their serum stability and biological activities.The results indicate that an N-Asn-linked complex-type sialylundecasaccharide can increase the serum half-life and in vivo bioactivity of PTH peptides with a broad tolerance of modification sites.Further,hydrogen/deuterium exchange mass spectroscopy indicates that the larger-sized Nglycan can induce enhanced hydration dynamics in its surroundings,which may facilitate an improved resistance for the peptide against enzymatic proteolysis.This sialylundecasaccharide-based peptideengineering strategy has also been applied to glucagon-like peptide-1(7-37),leading to glycopeptides with enhanced hypoglycemic activity and acting time in vivo.Together,these results demonstrate the potential of using sialylated complextype N-glycan as a general engineering strategy for developing long-acting peptide therapeutics.
基金supported by NSFC-Shandong Joint Fund(No.U1606403)Innovation Project of Qingdao National Laboratory for Marine Science and Technology(No.2015ASKJ02)。
文摘HYL derived from the venom of the solitary bee Hylaeus signatus(Hymenoptera:Colletidae)is anα-helical antimicrobial peptide with 16 residues.To explore whether HYL can be applied in anti-tumor therapy,we synthesized HYL and further modified its structure by using a solid-phase synthesis method,and then evaluated their antitumor activities.Firstly,we identified the key residues of HYL by alanine scanning strategy,and then a series of stapled peptides were synthesized by hydrocarbon stapling strategy without destroying the key residues.All the stapled peptides of HYL showed significant improvement not only inα-helicity,but also in antitumor activity and protease resistance when compared to the parent peptide HYL.The results showed that hydrophobicity and amphiphilicity are important factors affecting the antitumor activity of HYL,and the stapling strategy can significantly affect the proteolytic stability and helicity of HYL.What’s more,we find that the stapled peptides HYL-14,HYL-16 and HYL-18 show a promising prospect for novel anti-tumor drug development.
文摘Hainantoxin-Ⅳ(HNTX-Ⅳ)was isolated from the Chinese bird spider Ornithoctorcs hainana and identified as a novel antagonist of tetrodotoxin-sensitive(TTX-S)sodium channels.As revealed by the solution structure of HNTX-Ⅳ solved by two-dimensional nuclear magnetic resonance(2D-NMR),HNTX-Ⅳ adopts an inhibitor cystine knot motif.To check the role of basic residues during HNTX-Ⅳ’s interaction with TTX-S sodium channels,R26A and K27A mutants of HNTX-Ⅳ were constructed by solid-phase chemical synthesis.The synthesized peptides were purified and refolded under optimized oxidation conditions.Correct synthesis and folding were confirmed by MALDI-TOF mass spectrometry and NMR spectroscopy,respectively.Using the whole-cell patch-clamp technique,Lys27 but not Arg26 was identified as a key residue for HNTX-Ⅳ’s bioactivity against TTX-S sodium channels,because R26A-HNTX-Ⅳ showed slightly reduced activity and K27A-HNTX-Ⅳ showed almost no inhibition.
