APTES-bounded MNP were prepared by chemical coprecipitation,followed by coating with((γ-aminopropyl))triethoxysilane.Norvancomycin hydrochloride(Van) was then immobilized onto the amino-functionalized nanopartiles.Po...APTES-bounded MNP were prepared by chemical coprecipitation,followed by coating with((γ-aminopropyl))triethoxysilane.Norvancomycin hydrochloride(Van) was then immobilized onto the amino-functionalized nanopartiles.Powder X-ray diffraction(XRD) results show the inverse spinel structure of MNP.The physics property measurement system(PPMS) indicates that the MNP are superparamagnetic.The presence of Van and APTES on the surface of MNP is confirmed by FTIR.By a separation assay of S.aureus and E.coli BL21,it is proved that MNP-APTES-Van can selectively capture S.aureus within 10 min,which can be isolated readily by applying an external magnetic field.展开更多
The synthesis of norvancomycin (NVan)-capped silver nanoparticles (Ag@NVan) and their notable in vitro antibacterial activities against E. coli, a Gram-negative bacterial strain (GNB), are reported here. Mercaptoaceti...The synthesis of norvancomycin (NVan)-capped silver nanoparticles (Ag@NVan) and their notable in vitro antibacterial activities against E. coli, a Gram-negative bacterial strain (GNB), are reported here. Mercaptoacetic acid-stabilized spherical silver nanoparticles with a diameter of 16±4 nm are prepared by a simple chemical reaction. The formation process of the silver nanoparticles is investigated by UV-visible (UV-vis) spectroscopy and transmission electron microscopy (TEM). NVan is then grafted to the terminal carboxyl of the mercaptoacetic acid in the presence of N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC). The TEM images of single bacteria treated with Ag@NVan show that plenty of Ag@NVan aggregate in the cell wall of E. coli. A possible antibacterial mechanism is proposed that silver nanoparticles may help destroy the stability of the outer membrane of E. coli, which makes NVan easier to bind to the nether part of the peptidoglycan structure. The antibacterial activities of silver nanoparticles on their own, together with the rigid polyvalent interaction between Ag@NVan and cell wall, enables Ag@NVan to be an effective inhibitor of GNB. This kind of bionanocomposites might be used as novel bactericidal materials and we also provide an effective synthesis method for preparing functional bioconjugated nanoparticles here.展开更多
Nucleases play an important role in molecular biology, for example, in DNA sequencing. Synthetic polyamide conjugates can be considered as a novel tool for the selective inhibition of gene expressions and also as pote...Nucleases play an important role in molecular biology, for example, in DNA sequencing. Synthetic polyamide conjugates can be considered as a novel tool for the selective inhibition of gene expressions and also as potential drugs in anticancer or antiviral chemotherapy. In this article, the synthesis of a novel minor-groove targeting artificial nuclease, an oligopyrrol-containing compound, has been reported. It was found that this novel compound can bind DNA in AT-rich minor groove with high affinity and site specificity. DNA binding behavior was determined by using UV-Vis and CD. It is indicated that compound 6 can enhance the Tm, of DNA from 80.4 ℃ to 84. 4 ℃ and that it possesses a high binding constant value（Kb =3.05 × 10^4 L/mol）.展开更多
Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmo...Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSALDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2%and 94.8%,respectively(P<0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.展开更多
Herein,we report the facile conjugation between proteins and water-soluble [60]fullerene derivatives(DC_(60)) under native conditions using SpyTag as a reactive handle.Water-soluble [60] fullerene derivatives were fir...Herein,we report the facile conjugation between proteins and water-soluble [60]fullerene derivatives(DC_(60)) under native conditions using SpyTag as a reactive handle.Water-soluble [60] fullerene derivatives were first prepared via sequential Bingel-Hirsch reaction and "clicked" with SpyTag to give DC_(60)-SpyTag for native conjugation with proteins by the highly efficient SpyTag-SpyCatcher chemistry.The bioconjugation was confirmed by MALDI-TOF MS spectra and SDS-PAGE analysis.The TEM and UVvis spectroscopic study further revealed that the DC_(60) could alter the optical performance and induce aggregation of the target proteins.It thus provides a general and robust method for modifying proteins with C_(60) derivatives and could potentially be adapted for native conjugation between proteins and other nonbiological motifs as well.展开更多
L-Tyr-EMPO,a new EMPO analogue bearing an L-tyrosine methyl ether group,was first synthesized by acylation.Various radicals,including O-·2,·OH,·OR,and ·R,have been efficiently detected and characte...L-Tyr-EMPO,a new EMPO analogue bearing an L-tyrosine methyl ether group,was first synthesized by acylation.Various radicals,including O-·2,·OH,·OR,and ·R,have been efficiently detected and characterized via L-Tyr-EMPO.The half-life of the L-Tyr-EMPO superoxide adduct was estimated to be ca.6.5 min.More importantly,the present study demonstrated a new synthetic strategy for covalent conjugation between cyclic-nitrone and amino group in peptides or proteins,by which the site-specifically spin trapping can be performed via antibody linked nitrone in the near future.Furthermore,with the help of the covalent link,the targeting for the areas of interest in which the monitored radical species was sitespecially generated.展开更多
One of the main goals of vaccine research is the development of adjuvants that can enhance immune responses and are both safe and biocompatible.We explored the application of the natural polymer hyaluronan(HA)as a pro...One of the main goals of vaccine research is the development of adjuvants that can enhance immune responses and are both safe and biocompatible.We explored the application of the natural polymer hyaluronan(HA)as a promising immunological adjuvant for protein-based vaccines.Chemical conjugation of HA to antigens strongly increased their immunogenicity,reduced booster requirements,and allowed antigen dose sparing.HA-based bioconjugates stimulated robust and long-lasting humoral responses without the addition of other immunostimulatory compounds and proved highly efficient when compared to other adjuvants.Due to its intrinsic biocompatibility,HA allowed the exploitation of different injection routes and did not induce inflammation at the inoculation site.This polymer promoted rapid translocation of the antigen to draining lymph nodes,thus facilitating encounters with antigen-presenting cells.Overall,HA can be regarded as an effective and biocompatible adjuvant to be exploited for the design of a wide variety of vaccines.展开更多
文摘APTES-bounded MNP were prepared by chemical coprecipitation,followed by coating with((γ-aminopropyl))triethoxysilane.Norvancomycin hydrochloride(Van) was then immobilized onto the amino-functionalized nanopartiles.Powder X-ray diffraction(XRD) results show the inverse spinel structure of MNP.The physics property measurement system(PPMS) indicates that the MNP are superparamagnetic.The presence of Van and APTES on the surface of MNP is confirmed by FTIR.By a separation assay of S.aureus and E.coli BL21,it is proved that MNP-APTES-Van can selectively capture S.aureus within 10 min,which can be isolated readily by applying an external magnetic field.
基金Supported by the National Natural Science Foundation of China (Grant No. 50373036)Fok Ying Tung Education Foundation (Grant No. J20040212)
文摘The synthesis of norvancomycin (NVan)-capped silver nanoparticles (Ag@NVan) and their notable in vitro antibacterial activities against E. coli, a Gram-negative bacterial strain (GNB), are reported here. Mercaptoacetic acid-stabilized spherical silver nanoparticles with a diameter of 16±4 nm are prepared by a simple chemical reaction. The formation process of the silver nanoparticles is investigated by UV-visible (UV-vis) spectroscopy and transmission electron microscopy (TEM). NVan is then grafted to the terminal carboxyl of the mercaptoacetic acid in the presence of N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC). The TEM images of single bacteria treated with Ag@NVan show that plenty of Ag@NVan aggregate in the cell wall of E. coli. A possible antibacterial mechanism is proposed that silver nanoparticles may help destroy the stability of the outer membrane of E. coli, which makes NVan easier to bind to the nether part of the peptidoglycan structure. The antibacterial activities of silver nanoparticles on their own, together with the rigid polyvalent interaction between Ag@NVan and cell wall, enables Ag@NVan to be an effective inhibitor of GNB. This kind of bionanocomposites might be used as novel bactericidal materials and we also provide an effective synthesis method for preparing functional bioconjugated nanoparticles here.
基金Supported by the National Natural Science Foundation of China(Nos 20132020 and 20572061), the National Science andTechnology Committee of China, the National Ministry of Education of China, and Tsinghua University
文摘Nucleases play an important role in molecular biology, for example, in DNA sequencing. Synthetic polyamide conjugates can be considered as a novel tool for the selective inhibition of gene expressions and also as potential drugs in anticancer or antiviral chemotherapy. In this article, the synthesis of a novel minor-groove targeting artificial nuclease, an oligopyrrol-containing compound, has been reported. It was found that this novel compound can bind DNA in AT-rich minor groove with high affinity and site specificity. DNA binding behavior was determined by using UV-Vis and CD. It is indicated that compound 6 can enhance the Tm, of DNA from 80.4 ℃ to 84. 4 ℃ and that it possesses a high binding constant value（Kb =3.05 × 10^4 L/mol）.
基金supported by grants from CAMS Innovation Fund for Medical Sciences(Grant No.:2021-I2M-1-026)Scientific Research Project of Tianjin Education Commission(Grant No.:2020KJ140)Tianjin Health Research Project(Grant No.:KJ20017)。
文摘Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSALDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2%and 94.8%,respectively(P<0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.
基金the financial support from the National Natural Science Foundation of China(Nos.21925102,21991132 and 21674003)supported by Beijing National Laboratory for Molecular Sciences(No.BNLMS-CXXM-202006)Clinical Medicine Plus X Project of Peking University,Fundamental Research Funds for the Central Universities。
文摘Herein,we report the facile conjugation between proteins and water-soluble [60]fullerene derivatives(DC_(60)) under native conditions using SpyTag as a reactive handle.Water-soluble [60] fullerene derivatives were first prepared via sequential Bingel-Hirsch reaction and "clicked" with SpyTag to give DC_(60)-SpyTag for native conjugation with proteins by the highly efficient SpyTag-SpyCatcher chemistry.The bioconjugation was confirmed by MALDI-TOF MS spectra and SDS-PAGE analysis.The TEM and UVvis spectroscopic study further revealed that the DC_(60) could alter the optical performance and induce aggregation of the target proteins.It thus provides a general and robust method for modifying proteins with C_(60) derivatives and could potentially be adapted for native conjugation between proteins and other nonbiological motifs as well.
文摘L-Tyr-EMPO,a new EMPO analogue bearing an L-tyrosine methyl ether group,was first synthesized by acylation.Various radicals,including O-·2,·OH,·OR,and ·R,have been efficiently detected and characterized via L-Tyr-EMPO.The half-life of the L-Tyr-EMPO superoxide adduct was estimated to be ca.6.5 min.More importantly,the present study demonstrated a new synthetic strategy for covalent conjugation between cyclic-nitrone and amino group in peptides or proteins,by which the site-specifically spin trapping can be performed via antibody linked nitrone in the near future.Furthermore,with the help of the covalent link,the targeting for the areas of interest in which the monitored radical species was sitespecially generated.
基金supported by Fondazione AIRC under IG 2018-ID.21354 project-P.I.Rosato Antonio,5 per Mille 2019-ID.22759 program-G.L.Rosato Antonio,BIGID219MON2 from 5 per Mille 2018Veneto Institute of Oncology IOV-IRCCS to I.M.M.,Bando Ricerca Covid 2019 from Fondazione Cassa di Risparmio di Padova e Rovigo.P.D.B.wishes to thank the Italian Ministry of Health,which partially contributed to the achievements of the study through RC IZSVE 08/06.
文摘One of the main goals of vaccine research is the development of adjuvants that can enhance immune responses and are both safe and biocompatible.We explored the application of the natural polymer hyaluronan(HA)as a promising immunological adjuvant for protein-based vaccines.Chemical conjugation of HA to antigens strongly increased their immunogenicity,reduced booster requirements,and allowed antigen dose sparing.HA-based bioconjugates stimulated robust and long-lasting humoral responses without the addition of other immunostimulatory compounds and proved highly efficient when compared to other adjuvants.Due to its intrinsic biocompatibility,HA allowed the exploitation of different injection routes and did not induce inflammation at the inoculation site.This polymer promoted rapid translocation of the antigen to draining lymph nodes,thus facilitating encounters with antigen-presenting cells.Overall,HA can be regarded as an effective and biocompatible adjuvant to be exploited for the design of a wide variety of vaccines.
