The development of artificial light-harvesting systems based on long-range ordered ultrathin organic nanomaterials(i.e., below3 nm), which were assembled from stimuli-responsive sequence-controlled biomimetic polymers...The development of artificial light-harvesting systems based on long-range ordered ultrathin organic nanomaterials(i.e., below3 nm), which were assembled from stimuli-responsive sequence-controlled biomimetic polymers, remains challenging. Herein,we report the self-assembly of azobenzene-containing amphiphilic ternary alternating peptoids to construct photo-responsive ultrathin peptoids nanoribbons(UTPNRs) with a thickness of ~2.3 nm and the length in several micrometers. The pendants hydrophobic conjugate stacking mechanism explained the formation of one-dimensional ultrathin nanostructures, whose thickness was highly dependent on the length of side groups. The photo-isomerization of azobenzene moiety endowed the aggregates with a reversible morphology transformation from UTPNRs to spherical micelles(46.5 nm), upon the alternative irradiation with ultraviolet and visible light. Donor of 4-(2-hydroxyethylamino)-7-nitro-2,1,3-benzoxadiazole(NBD) and acceptor of rhodamine B(RB) were introduced onto the hydrophobic and hydrophilic regions, respectively, to generate photocontrollable artificial light-harvesting systems. Compared with the spheres-based systems, the obtained NBD-UTPNRs@RB composite proved a higher energy transfer efficiency(90.6%) and a lower requirement of RB acceptors in water. A proof-ofconcept use as fluorescent writable ink demonstrated the potential of UTPNRs on information encryption.展开更多
Precisely controlled spatial distributions of artificial light-harvesting systems in aqueous media are of significant importance for mimicking natural light-harvesting systems;however,they are often restrained by the ...Precisely controlled spatial distributions of artificial light-harvesting systems in aqueous media are of significant importance for mimicking natural light-harvesting systems;however,they are often restrained by the solubility and the aggregation-caused quenching effect of the hydrophobic chromophores.Herein,we report one highly efficient artificial light-harvesting system based on peptoid nanotubes that mimic the hierarchical cylindrical structure of natural systems.The high crystallinity of these nanotubes enabled the organization of arrays of donor chromophores with precisely controlled spatial distributions,favoring an efficient Förster resonance energy transfer(FRET)process in aqueous media.This FRET system exhibits an extremely high efficiency of 98.6%with a fluorescence quantum yield of 40%and an antenna effect of 29.9.We further demonstrated the use of this artificial light-harvesting system for quantifying miR-210 within cancer cells.The fluorescence intensity ratio of donor to acceptor is linearly related to the concentration of intercellular miR-210 in the range of 3.3–156 copies/cell.Such high sensitivity in intracellular detection of miR-210 using this artificial light-harvesting system offers a great opportunity and pathways for biological imaging and detection,and for the further creation of microRNA(miRNA)toolbox for quantitative epigenetics and personalized medicine.展开更多
CD28 is one of the costimulatory molecules crucial for T-cell activation and thus has become an attractive target for therapeutic immunomodulation. Conventional strategies for blocking CD28 activity using monoclonal a...CD28 is one of the costimulatory molecules crucial for T-cell activation and thus has become an attractive target for therapeutic immunomodulation. Conventional strategies for blocking CD28 activity using monoclonal antibodies, Fab fragments, antagonistic peptide and fusion proteins, have apparent disadvantages such as inherent immunogenicity, unwanted Fc signaling, poor tissue penetration and bioinstability. Recent research has been directed toward the creation of non-natural, sequence-specific biomimetic oligomers with bioinspired structures that capture the amino-acid interface of the targeted proteins. One such family of molecules is the poly-N-substituted glycines or peptoids, which have close structural similarity to peptides but are essentially invulnerable to protease degradation. To screen for peptoids that specifically target CD28, we first designed and chemically synthesized 19 candidate peptoids based on molecular modeling and docking. Using the phage-displaying system that expresses the extracellular domain of the CD28 homodimer and contains the core B7-binding motif, a peptoid （No. 9） with a molecular formula of C21H29N307, was identified to display the highest binding activity to CD28. This peptoid not only inhibited the lymphocyte proliferation in vitro, but suppressed immunoresponses against alloantigens in vivo, and attenuated the graft-versus-host disease in a mouse bone-marrow transplantation model. These results suggested that peptoids targeting CD28 are effective agents for blocking the CD28-mediated costimulation and suitable for development of novel therapeutic approaches for diseases involving this pathway.展开更多
The synthesis of peptoid nucleic acid bearing thymine as nucleobase has been achieved. This modified oligonucleotide showed good hybridization with DNA.
Eight peptoid chiral stationary phases （CSPs） terminated with N＇substituted phenyl-L-proline or L-leucine amide were prepared and evaluated under normal phase mode. With 59 racemic analytes, we compared the enantio...Eight peptoid chiral stationary phases （CSPs） terminated with N＇substituted phenyl-L-proline or L-leucine amide were prepared and evaluated under normal phase mode. With 59 racemic analytes, we compared the enantio- meric separations on CSPs terminated with p-methylphenyl, p-chlorophenyl and unsubstituted phenyl. For short peptoid selectors containing only one S-N-（1-phenylethyl） glycine （Nspe） unit, the terminal p-methyl substituent did not affect chiral recognition abilities significantly. In L-proline amide terminated CSPs, p-chloro substituent resulted in obviously inferior selectivity while in L-leucine amide terminated CSPs, it worked much better. Longer peptoid selectors containing two more Nspe units generally performed much better than the shorter ones, due to the great contributions of peptoid chain to chiral recognition. Meanwhile, the effects of the terminal substituent on selectivity were found changed on these CSPs. For CSPs terminated with L-leucine amide, the terminal p-chloro substituent in longer selector no longer produced the best recognition ability; the CSP with unsubstituted phenyl instead performed best. Comparison of these peptoid CSPs varied in terminal substituents and chain length was conducted to gain a better understanding of the chiral recognition mechanism of this type CSP and promote the development of more useful CSPs.展开更多
Artificial vesicles for mimicking the unique structures and functions of natural organelles represent a promising scientific object in biomimicry.However,the development of the stimuli-responsive and ultrathin vesicle...Artificial vesicles for mimicking the unique structures and functions of natural organelles represent a promising scientific object in biomimicry.However,the development of the stimuli-responsive and ultrathin vesicles assembled from sequence-defined biomimetic polymers for controllable applications is still a significant challenge.Herein,we report the self-assembly of azobenzene-based amphiphilic alternating peptoids to generate photo-responsive and ultrathin peptoid vesicle(pepsomes)with an average diameter of∼180 nm.Both cryo-transmission electron microscopy(TEM)and dissipative particle dynamics simulation proved that the vesicular membrane was the ultrathin bilayer structure around∼1.6 nm.The photo-responsive ability of pepsomes was demonstrated by the reversible size changes upon the alternative irradiation with ultraviolet(UV)and visible lights,which was attributable to the photoisomerization virtue of azobenzene moiety.As a proof-of-concept,the photo-controllable catalytic action of gold nanoparticles-decorated pepsomes was evaluated toward the borohydride-mediated reduction from 4-nitrophenol to 4-aminophenol.Photo-controllable reversible and recyclable catalytic activity was effectively modulated using the alternative irradiation with UV and visible lights for five cycles.Our work provides a simple strategy to prepare stimuli-responsive and ultrathin vesicles for potential application on nanocatalysis.展开更多
Peptoids(or poly-N-substituted glycines)are a promising class of bioinspired sequence-defined polymers due to their highly efficient synthesis,high chemical stability,enzyme hydrolysis resistance,and biocompatibility....Peptoids(or poly-N-substituted glycines)are a promising class of bioinspired sequence-defined polymers due to their highly efficient synthesis,high chemical stability,enzyme hydrolysis resistance,and biocompatibility.By tuning the side chain chemistry of peptoids,it allows for precise control over sequences and achieving a large side-chain diversity.Due to these unique features,in the last several years,many amphiphilic peptoids were designed as highly tunable building blocks for the preparation of biomimetic nanomaterials with well-defined hierarchical structures and desired functionalities.Herein,we provide an overview of the recent achievements in this area by dividing them into the following three aspects.First,mica-and silica-templated peptoid selfassembly are summarized.The presence of inorganic substrates provides the guarantee of investigating their selfassembly mechanisms and interactions between peptoids and substrates using nanoscale characterization techniques,particularly in situ atomic force microscopy(AFM)and AFMbased dynamic force spectroscopy(AFM-DFS).Second,solution-phase self-assembly of peptoids into nanotubes and nanosheets is presented,as well as their self-repair properties.Third,the applications of peptoid-based nanomaterials are outlined,including the construction of catalytic nanomaterials as a template and cytosolic delivery as cargoes.展开更多
Poly(β-peptoid)is a class of polypeptide mimics that possesses excellent biocompatibility and resistance to proteolysis.However,the synthesis of poly(β-peptoid)s with functionalities is a long-standing challenge tha...Poly(β-peptoid)is a class of polypeptide mimics that possesses excellent biocompatibility and resistance to proteolysis.However,the synthesis of poly(β-peptoid)s with functionalities is a long-standing challenge that greatly hinders the functional study and application of poly(β-peptoid)s.We report a controllable and easy synthesis of poly(β-peptoid)s bearing diverse functionalities via the ring-opening polymerization on N-substitutedβ-alanine N-thiocarboxyanhydrides(β-NNTAs).The polymerization can be carried out in openvesselsundermildconditions usingaminesas the initiators to provide poly(β-peptoid)s with targeted molecular weights,narrow dispersities,and diverse functionalities in the side chains and termini.Theβ-NNTAs polymerization is even compatible with initiators bearing unprotected hydroxyl groups.The amphiphilic/cationic poly(β-peptoid)s exhibit a broad spectrum and potent antibacterial activities against multidrug-resistant bacteria.In addition,the highly favored stability ofβ-NNTAmonomers for purification and storage highlights the advantages of thisβ-NNTA polymerization strategy for poly(β-peptoid)s synthesis,functional study,and application as a synthetic mimic of polypeptides.展开更多
相较于传统的抗体检测,适配体更易于大量快速合成,且可和多种检测技术相结合,在蛋白检测方面具有巨大的潜力.水孔蛋白作为生物体内水分跨膜运输的主要途径,了解其表达量的变化在植物水代谢研究中有着重要意义.利用传统的混合列分法构建...相较于传统的抗体检测,适配体更易于大量快速合成,且可和多种检测技术相结合,在蛋白检测方面具有巨大的潜力.水孔蛋白作为生物体内水分跨膜运输的主要途径,了解其表达量的变化在植物水代谢研究中有着重要意义.利用传统的混合列分法构建了8个C端恒定半胱氨酸残基的类肽适配体文库,结合表面等离激元共振成像技术,筛选得到能特异性结合高等植物水孔蛋白PIP2的类肽适配体PPA7,其亲和力 K D高达2.52×10 -9 mol/L.利用PPA7检测了石竹玻璃化和正常植株的水孔蛋白表达量,结果表明,石竹玻璃化植株的水孔蛋白表达量显著高于正常植株.研究提供了一种新的植物蛋白定量检测策略,也为进一步明确水孔蛋白在组培苗玻璃化发生中的作用奠定了基础.展开更多
基金supported by the National Natural Science Foundation of China (22001071, 52373114, 52073092, 52325308)Shanghai Scientific and Technological Innovation Project(19JC1411700)。
文摘The development of artificial light-harvesting systems based on long-range ordered ultrathin organic nanomaterials(i.e., below3 nm), which were assembled from stimuli-responsive sequence-controlled biomimetic polymers, remains challenging. Herein,we report the self-assembly of azobenzene-containing amphiphilic ternary alternating peptoids to construct photo-responsive ultrathin peptoids nanoribbons(UTPNRs) with a thickness of ~2.3 nm and the length in several micrometers. The pendants hydrophobic conjugate stacking mechanism explained the formation of one-dimensional ultrathin nanostructures, whose thickness was highly dependent on the length of side groups. The photo-isomerization of azobenzene moiety endowed the aggregates with a reversible morphology transformation from UTPNRs to spherical micelles(46.5 nm), upon the alternative irradiation with ultraviolet and visible light. Donor of 4-(2-hydroxyethylamino)-7-nitro-2,1,3-benzoxadiazole(NBD) and acceptor of rhodamine B(RB) were introduced onto the hydrophobic and hydrophilic regions, respectively, to generate photocontrollable artificial light-harvesting systems. Compared with the spheres-based systems, the obtained NBD-UTPNRs@RB composite proved a higher energy transfer efficiency(90.6%) and a lower requirement of RB acceptors in water. A proof-ofconcept use as fluorescent writable ink demonstrated the potential of UTPNRs on information encryption.
基金supported by the U.S.Department of Energy,Office of Basic Energy Sciences,Division of Materials Science and Engineering under an award FWP 65357 at Pacific Northwest National Laboratory(PNNL)the Cougar Cage Fund for the work of biological imaging and detection of microRNA.Development of peptoid synthesis capabilities was supported by the Materials Synthesis and Simulation Across Scales(MS3)Initiative through the Laboratory Directed Research and Development(LDRD)program at PNNL.XRD work was conducted at the Advanced Light Source(ALS)of Lawrence Berkeley National Laboratory+1 种基金supported by the Office of Science(No.DE-AC02-05CH11231)PNNL is multi-program national laboratory operated for Department of Energy by Battelle(No.DE-AC05-76RL01830).
文摘Precisely controlled spatial distributions of artificial light-harvesting systems in aqueous media are of significant importance for mimicking natural light-harvesting systems;however,they are often restrained by the solubility and the aggregation-caused quenching effect of the hydrophobic chromophores.Herein,we report one highly efficient artificial light-harvesting system based on peptoid nanotubes that mimic the hierarchical cylindrical structure of natural systems.The high crystallinity of these nanotubes enabled the organization of arrays of donor chromophores with precisely controlled spatial distributions,favoring an efficient Förster resonance energy transfer(FRET)process in aqueous media.This FRET system exhibits an extremely high efficiency of 98.6%with a fluorescence quantum yield of 40%and an antenna effect of 29.9.We further demonstrated the use of this artificial light-harvesting system for quantifying miR-210 within cancer cells.The fluorescence intensity ratio of donor to acceptor is linearly related to the concentration of intercellular miR-210 in the range of 3.3–156 copies/cell.Such high sensitivity in intracellular detection of miR-210 using this artificial light-harvesting system offers a great opportunity and pathways for biological imaging and detection,and for the further creation of microRNA(miRNA)toolbox for quantitative epigenetics and personalized medicine.
文摘CD28 is one of the costimulatory molecules crucial for T-cell activation and thus has become an attractive target for therapeutic immunomodulation. Conventional strategies for blocking CD28 activity using monoclonal antibodies, Fab fragments, antagonistic peptide and fusion proteins, have apparent disadvantages such as inherent immunogenicity, unwanted Fc signaling, poor tissue penetration and bioinstability. Recent research has been directed toward the creation of non-natural, sequence-specific biomimetic oligomers with bioinspired structures that capture the amino-acid interface of the targeted proteins. One such family of molecules is the poly-N-substituted glycines or peptoids, which have close structural similarity to peptides but are essentially invulnerable to protease degradation. To screen for peptoids that specifically target CD28, we first designed and chemically synthesized 19 candidate peptoids based on molecular modeling and docking. Using the phage-displaying system that expresses the extracellular domain of the CD28 homodimer and contains the core B7-binding motif, a peptoid （No. 9） with a molecular formula of C21H29N307, was identified to display the highest binding activity to CD28. This peptoid not only inhibited the lymphocyte proliferation in vitro, but suppressed immunoresponses against alloantigens in vivo, and attenuated the graft-versus-host disease in a mouse bone-marrow transplantation model. These results suggested that peptoids targeting CD28 are effective agents for blocking the CD28-mediated costimulation and suitable for development of novel therapeutic approaches for diseases involving this pathway.
基金Authors thank the National NatUral Science Foundation of China for financial support !(29672047).
文摘The synthesis of peptoid nucleic acid bearing thymine as nucleobase has been achieved. This modified oligonucleotide showed good hybridization with DNA.
文摘Eight peptoid chiral stationary phases （CSPs） terminated with N＇substituted phenyl-L-proline or L-leucine amide were prepared and evaluated under normal phase mode. With 59 racemic analytes, we compared the enantio- meric separations on CSPs terminated with p-methylphenyl, p-chlorophenyl and unsubstituted phenyl. For short peptoid selectors containing only one S-N-（1-phenylethyl） glycine （Nspe） unit, the terminal p-methyl substituent did not affect chiral recognition abilities significantly. In L-proline amide terminated CSPs, p-chloro substituent resulted in obviously inferior selectivity while in L-leucine amide terminated CSPs, it worked much better. Longer peptoid selectors containing two more Nspe units generally performed much better than the shorter ones, due to the great contributions of peptoid chain to chiral recognition. Meanwhile, the effects of the terminal substituent on selectivity were found changed on these CSPs. For CSPs terminated with L-leucine amide, the terminal p-chloro substituent in longer selector no longer produced the best recognition ability; the CSP with unsubstituted phenyl instead performed best. Comparison of these peptoid CSPs varied in terminal substituents and chain length was conducted to gain a better understanding of the chiral recognition mechanism of this type CSP and promote the development of more useful CSPs.
基金supported by the National Natural Science Foundation of China(52073092,22001071,51873061)Shanghai Scientific and Technological Innovation Projects(19JC1411700,18JC1410802)。
文摘Artificial vesicles for mimicking the unique structures and functions of natural organelles represent a promising scientific object in biomimicry.However,the development of the stimuli-responsive and ultrathin vesicles assembled from sequence-defined biomimetic polymers for controllable applications is still a significant challenge.Herein,we report the self-assembly of azobenzene-based amphiphilic alternating peptoids to generate photo-responsive and ultrathin peptoid vesicle(pepsomes)with an average diameter of∼180 nm.Both cryo-transmission electron microscopy(TEM)and dissipative particle dynamics simulation proved that the vesicular membrane was the ultrathin bilayer structure around∼1.6 nm.The photo-responsive ability of pepsomes was demonstrated by the reversible size changes upon the alternative irradiation with ultraviolet(UV)and visible lights,which was attributable to the photoisomerization virtue of azobenzene moiety.As a proof-of-concept,the photo-controllable catalytic action of gold nanoparticles-decorated pepsomes was evaluated toward the borohydride-mediated reduction from 4-nitrophenol to 4-aminophenol.Photo-controllable reversible and recyclable catalytic activity was effectively modulated using the alternative irradiation with UV and visible lights for five cycles.Our work provides a simple strategy to prepare stimuli-responsive and ultrathin vesicles for potential application on nanocatalysis.
基金supported by the Startup Research Fund of Dongguan University of Technology(KCYKYQD2017015)the US Department of Energy,Office of Science,Office of Basic Energy Sciences,as part of the Energy Frontier Research Centers program:CSSAS—The Center for the Science of Synthesis Across Scales(DESC0019288)。
文摘Peptoids(or poly-N-substituted glycines)are a promising class of bioinspired sequence-defined polymers due to their highly efficient synthesis,high chemical stability,enzyme hydrolysis resistance,and biocompatibility.By tuning the side chain chemistry of peptoids,it allows for precise control over sequences and achieving a large side-chain diversity.Due to these unique features,in the last several years,many amphiphilic peptoids were designed as highly tunable building blocks for the preparation of biomimetic nanomaterials with well-defined hierarchical structures and desired functionalities.Herein,we provide an overview of the recent achievements in this area by dividing them into the following three aspects.First,mica-and silica-templated peptoid selfassembly are summarized.The presence of inorganic substrates provides the guarantee of investigating their selfassembly mechanisms and interactions between peptoids and substrates using nanoscale characterization techniques,particularly in situ atomic force microscopy(AFM)and AFMbased dynamic force spectroscopy(AFM-DFS).Second,solution-phase self-assembly of peptoids into nanotubes and nanosheets is presented,as well as their self-repair properties.Third,the applications of peptoid-based nanomaterials are outlined,including the construction of catalytic nanomaterials as a template and cytosolic delivery as cargoes.
基金supported by the National Natural Science Foundation of China(nos.22075078 and 21861162010)the Free Exploring Basic Research Project at Shenzhen Research Institute of ECUST(no.2021Szvup042)+4 种基金the Program of Shanghai Academic/Technology Research Leader(no.20XD1421400)the National Natural Science Foundation of China for Innovative Research Groups(no.51621002)the China National Postdoctoral Program for Innovative Talents(no.BX2021102)the Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission,grant 2021 Sci&Tech 03-28)the Research Program of the State Key Laboratory of Bioreactor Engineering,the Fundamental Research Funds for the Central Universities(no.JKD01211520).
文摘Poly(β-peptoid)is a class of polypeptide mimics that possesses excellent biocompatibility and resistance to proteolysis.However,the synthesis of poly(β-peptoid)s with functionalities is a long-standing challenge that greatly hinders the functional study and application of poly(β-peptoid)s.We report a controllable and easy synthesis of poly(β-peptoid)s bearing diverse functionalities via the ring-opening polymerization on N-substitutedβ-alanine N-thiocarboxyanhydrides(β-NNTAs).The polymerization can be carried out in openvesselsundermildconditions usingaminesas the initiators to provide poly(β-peptoid)s with targeted molecular weights,narrow dispersities,and diverse functionalities in the side chains and termini.Theβ-NNTAs polymerization is even compatible with initiators bearing unprotected hydroxyl groups.The amphiphilic/cationic poly(β-peptoid)s exhibit a broad spectrum and potent antibacterial activities against multidrug-resistant bacteria.In addition,the highly favored stability ofβ-NNTAmonomers for purification and storage highlights the advantages of thisβ-NNTA polymerization strategy for poly(β-peptoid)s synthesis,functional study,and application as a synthetic mimic of polypeptides.
文摘相较于传统的抗体检测,适配体更易于大量快速合成,且可和多种检测技术相结合,在蛋白检测方面具有巨大的潜力.水孔蛋白作为生物体内水分跨膜运输的主要途径,了解其表达量的变化在植物水代谢研究中有着重要意义.利用传统的混合列分法构建了8个C端恒定半胱氨酸残基的类肽适配体文库,结合表面等离激元共振成像技术,筛选得到能特异性结合高等植物水孔蛋白PIP2的类肽适配体PPA7,其亲和力 K D高达2.52×10 -9 mol/L.利用PPA7检测了石竹玻璃化和正常植株的水孔蛋白表达量,结果表明,石竹玻璃化植株的水孔蛋白表达量显著高于正常植株.研究提供了一种新的植物蛋白定量检测策略,也为进一步明确水孔蛋白在组培苗玻璃化发生中的作用奠定了基础.
