Using scanning tunneling microscopy we observe a stripe phase smoothly interfacing with a triangular 2 ×2 super- structure on the surface of 2H-NbSe2 single crystM. Proximity-induced superconductivity is demonstr...Using scanning tunneling microscopy we observe a stripe phase smoothly interfacing with a triangular 2 ×2 super- structure on the surface of 2H-NbSe2 single crystM. Proximity-induced superconductivity is demonstrated in these new ordered structures by measurements of low-temperature tunneling spectra. The modulation of superconduc- tivity by the reconstruction provides an opportunity to understand the interplay between superconductivity and charge orders.展开更多
Whilst most bioorthogonal reactions focus on targeting binding-site cysteine residues,proximity-induced reactivity effect ensures that reaction also occurs at nucleophilic lysine residues.We report one example here th...Whilst most bioorthogonal reactions focus on targeting binding-site cysteine residues,proximity-induced reactivity effect ensures that reaction also occurs at nucleophilic lysine residues.We report one example here that the propargylated-sulfonium center undergoes a nucleophilic reaction with lysine residue via proximity-induced conjugation.This propargylated-sulfonium tethered peptide resulting from a facile propargylation of thiolethers,enables amino-yne reaction at the selected lysine on MDM4 protein.This strategy represents a viable approach of lysine-targeted covalent inhibition in proximity.展开更多
We observed a novel voltage peak in the proximity-induced superconducting gold(Au) nanowire while cooling the sample through the superconducting transition temperature. The voltage peak turned dip during warming. The ...We observed a novel voltage peak in the proximity-induced superconducting gold(Au) nanowire while cooling the sample through the superconducting transition temperature. The voltage peak turned dip during warming. The voltage peak or dip was found to originate respectively from the emergence or vanishing of the proximity-induced superconductivity in the Au nanowire.The amplitude of the voltage signal depends on the temperature scanning rate, and it cannot be detected when the temperature is changed slower than 0.03 K/min. This transient feature suggests the non-equilibrium property of the effect. Ginzburg-Landau model clarified the voltage peak by considering the emergence of Cooper pairs of relatively lower free energy in superconducting W contact and the non-equilibrium diffusion of Cooper pairs and quasiparticles.展开更多
Targeted protein degradation(TPD)represented by proteolysis targeting chimeras(PROTACs)marks a significant stride in drug discovery.A plethora of innovative technologies inspired by PROTAC have not only revolutionized...Targeted protein degradation(TPD)represented by proteolysis targeting chimeras(PROTACs)marks a significant stride in drug discovery.A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond degradation.Non-small-molecule-based approaches play an irreplaceable role in this field.A wide variety of agents spanning a broad chemical spectrum,including peptides,nucleic acids,antibodies,and even vaccines,which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing paradigms.Herein we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs,including three major trajectories,to provide insights for the design strategies based on novel paradigms.展开更多
The modification and functionalization of peptides is of great significance in modern biotechnology and drug development. Here we report a highly reactive Michael-type warhead for the covalently modification of cystei...The modification and functionalization of peptides is of great significance in modern biotechnology and drug development. Here we report a highly reactive Michael-type warhead for the covalently modification of cysteine on peptide and protein. By installing a vinyl group onto a methionine residue of peptide,the produced vinyl sulfonium can be efficiently nucleophilic added by appropriate cysteine residue of this peptide, and thus yield a cyclized peptide. This peptide cyclization strategy was proven to exhibit improved cell penetration and good stability. Moreover, a peptide ligand bearing vinyl sulfonium could covalently bind to the cysteine in the target protein, indicating the potential of vinyl sulfonium as a novel warhead for developing covalent peptide inhibitor.展开更多
基金Supported by the National Natural Science Foundation of China under Grant Nos 11574372 and 11322432the 'Strategic Priority Research Program(B)' of the Chinese Academy of Sciences under Grant No XDB07020300
文摘Using scanning tunneling microscopy we observe a stripe phase smoothly interfacing with a triangular 2 ×2 super- structure on the surface of 2H-NbSe2 single crystM. Proximity-induced superconductivity is demonstrated in these new ordered structures by measurements of low-temperature tunneling spectra. The modulation of superconduc- tivity by the reconstruction provides an opportunity to understand the interplay between superconductivity and charge orders.
基金financial support from the National Key Research and Development Program"Synthetic Biology"Key Special Project of China(No.2018YFA0902504)the Natural Science Foundation of China(Nos.21778009 and 21977010)+6 种基金the Natural Science Foundation ofGuangdongProvince(Nos.2020A1515010766,2020A1515010522,2019A1515111184 and 2019A1515110489)the Shenzhen Science and Technology Innovation Committee(Nos.JCYJ20180507181527112,JCYJ20180508152213145,and JCYJ20170817172023838)financial support from Beijing National Laboratory of Molecular Science Open Grant(No.BNLMS20160112)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(No.2019SHIBS0004)supported by Proteomic Platform of Pingshan Translational Medicine CenterShenzhen Bay Laboratorythe high-performance computing platform of Peking University.
文摘Whilst most bioorthogonal reactions focus on targeting binding-site cysteine residues,proximity-induced reactivity effect ensures that reaction also occurs at nucleophilic lysine residues.We report one example here that the propargylated-sulfonium center undergoes a nucleophilic reaction with lysine residue via proximity-induced conjugation.This propargylated-sulfonium tethered peptide resulting from a facile propargylation of thiolethers,enables amino-yne reaction at the selected lysine on MDM4 protein.This strategy represents a viable approach of lysine-targeted covalent inhibition in proximity.
基金supported by the National Basic Research Program of China(Grant Nos.2017YFA0303300,and 2013CB934600)the National Natural Science Foundation of China(Grant No.11774008)+3 种基金the Open Research Fund Program of the State Key Laboratory of Low-Dimensional Quantum Physics(Grant No.KF201703)at Tsinghua University the Key Research Program of the Chinese Academy of Sciences(Grant No.XDPB08-1)the Peking University President’s Fund for Undergraduate Research(2013)Penn State was supported by NSF grants(MRSEC)(Grant Nos.DMR-0820404 and DMR-1420620)
文摘We observed a novel voltage peak in the proximity-induced superconducting gold(Au) nanowire while cooling the sample through the superconducting transition temperature. The voltage peak turned dip during warming. The voltage peak or dip was found to originate respectively from the emergence or vanishing of the proximity-induced superconductivity in the Au nanowire.The amplitude of the voltage signal depends on the temperature scanning rate, and it cannot be detected when the temperature is changed slower than 0.03 K/min. This transient feature suggests the non-equilibrium property of the effect. Ginzburg-Landau model clarified the voltage peak by considering the emergence of Cooper pairs of relatively lower free energy in superconducting W contact and the non-equilibrium diffusion of Cooper pairs and quasiparticles.
基金supported by grants from the National Natural Science Foundation of China(22177084,82273559,82103757 and 82073473)the China Postdoctoral Science Foundation(2022M722283)+2 种基金PostDoctor Research Project,West China Hospital,Sichuan University(2023HXBH076,China)Sichuan Natural Science Foundation Project(2023NSFSC1554,China)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21036,China).
文摘Targeted protein degradation(TPD)represented by proteolysis targeting chimeras(PROTACs)marks a significant stride in drug discovery.A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond degradation.Non-small-molecule-based approaches play an irreplaceable role in this field.A wide variety of agents spanning a broad chemical spectrum,including peptides,nucleic acids,antibodies,and even vaccines,which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing paradigms.Herein we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs,including three major trajectories,to provide insights for the design strategies based on novel paradigms.
基金financial support from the National Key Research and Development Program"Synthetic Biology"Key Special Project of China (No. 2018YFA0902504)the China Postdoctoral Science Foundation (No. 2021M690220)+7 种基金the National Natural Science Foundation of China (Nos. 21778009 and21977010)the Natural Science Foundation of Guangdong Province(Nos. 2019A1515110487, 2020A1515010522 and 2019A1515111184)the Shenzhen Science and Technology Innovation Committee (Nos. JCYJ20180507181527112, JCYJ20180508152213145, and JCYJ20170817172023838)the Foundation for Basic and Applied Research of Guangdong Province (No. 2019A1515110489)Guangdong Medical Science Foundation (No. A2021413)financial support from Beijing National Laboratory of Molecular Science Open Grant (No. BNLMS20160112)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions (No. 2019SHIBS0004)supported by the high-performance computing platform of Peking University。
文摘The modification and functionalization of peptides is of great significance in modern biotechnology and drug development. Here we report a highly reactive Michael-type warhead for the covalently modification of cysteine on peptide and protein. By installing a vinyl group onto a methionine residue of peptide,the produced vinyl sulfonium can be efficiently nucleophilic added by appropriate cysteine residue of this peptide, and thus yield a cyclized peptide. This peptide cyclization strategy was proven to exhibit improved cell penetration and good stability. Moreover, a peptide ligand bearing vinyl sulfonium could covalently bind to the cysteine in the target protein, indicating the potential of vinyl sulfonium as a novel warhead for developing covalent peptide inhibitor.