Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydroph...Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydrophobic interaction between the ligand(ThT) and substrate(Aβ1-42) are stronger than hydrogen bonds.Furthermore,ThT tends to be located near the C-terminus of Aβ monomer through hydrophobic and electrostatic interactions,while it tends to contact the residues Met35 and Gly27 of the fibril surface mainly through hydrophobic interaction.Finally,according to the docking results and ThT fluorescence assay,a kinetic equation is proposed to deduce the aggregation rate coefficient of Aβ1-42.展开更多
Numerous peptides derived from naturally occurring proteins or de novo designed have been found to self-assemble into various nanostructures.These well-defined nanostructures have shown great potential for a variety o...Numerous peptides derived from naturally occurring proteins or de novo designed have been found to self-assemble into various nanostructures.These well-defined nanostructures have shown great potential for a variety of biomedical and biotechnological applications.In particular,surfactant-like peptides(SLPs)have distinctive advantages in their length,aggregating ability,and water solubility.In this article,we report recent advances in the mechanistic understanding of the self-assembly principles of SLPs and in their applications,most of which have been made in our laboratory.Hydrogen bonding between peptide backbones,hydrophobic interaction between hydrophobic side chains,and electrostatic repulsion between charged head groups all have roles in mediating the self-assembly of SLPs;the final self-assembled nanostructures are therefore dependent on their interplay.SLPs have shown diverse applications ranging from membrane protein stabilization and antimicrobial/anticancer agents to nanofabrication and biomineralization.Future advances in the self-assembly of SLPs will hinge on their large-scale production,the design of new functional SLPs with targeted properties,and the exploitation of new or improved applications.展开更多
Smart peptide hydrogels are of great interest for their great potential applications. Here, we report a facile approach to prepare a class of enzyme-responsive hydrogels in a scalable manner. These hydrogels self-asse...Smart peptide hydrogels are of great interest for their great potential applications. Here, we report a facile approach to prepare a class of enzyme-responsive hydrogels in a scalable manner. These hydrogels self-assemble from a family of nonionic peptide amphiphiles(PAs) synthesized by sequential ring-opening polymerization(ROP) of γ-benzyl-L-glutamate N-carboxyanhydride(BLG-NCA) and L-tyrosine N-carboxyanhydride(Tyr-NCA), followed by subsequent aminolysis. These PA samples can readily form a clear hydrogel with a critical gelation concentration as low as 0.5 wt%. The incorporation of tyrosine residues offers hydrophobicity, hydrogen-bonding interaction and enzyme-responsive properties. The hydrogel-to-nanogel transition is observed under physiological conditions in the presence of horseradish peroxidase(HRP) and hydrogen peroxide(H2 O2). The obtained PA hydrogels are ideal candidates for the new generation of smart scaffolds.展开更多
Peptide-membrane binding is vital for many biological events,including the bacteria combating by antimicrobial peptides.Using the p H sensitive LAH4 peptide as model,we employed a convenient electron paramagnetic reso...Peptide-membrane binding is vital for many biological events,including the bacteria combating by antimicrobial peptides.Using the p H sensitive LAH4 peptide as model,we employed a convenient electron paramagnetic resonance(EPR)method to study the peptide-membrane binding process in artificial phospholipid membranes.Based on spectral changes of the nitroxide radical labeled to the peptides,we characterized binding kinetics and affinity of peptides to different phospholipid membranes.The binding affinity of LAH4 towards POPG was more than an order of magnitude higher than those towards DMPC and POPC.The binding kinetics showed that LAH4 initially bound to POPG much more quickly than to DMPC and POPC.Additionally,p H also affected the binding kinetics in LAH4-membrane interactions,which helped explain the p H dependent antimicrobial activity of LAH4.The method might be further used to monitor the membrane binding/cell penetration of antimicrobial peptide in living cells.展开更多
The binding energies of thirty-six hydrogen-bonded peptide-base complexes, including the peptide backbone-ase complexes and amino acid side chain-base complexes, are evaluated using the analytic potential energy funct...The binding energies of thirty-six hydrogen-bonded peptide-base complexes, including the peptide backbone-ase complexes and amino acid side chain-base complexes, are evaluated using the analytic potential energy function established in our lab recently and compared with those obtained from MP2, AMBER99, OPLSAA/L, and CHARMM27 calculations. The comparison indicates that the analytic potential energy function yields the binding energies for these complexes as reasonable as MP2 does, much better than the force fields do. The individual N H…O=C, N H…N, C H…O=C, and C H…N attractive interaction energies and C=O…O=C, N H…H N, C H…H N, and C H…H C repulsive interaction energies, which cannot be easily obtained from ab initio calculations, are calculated using the dipole-dipole interaction term of the analytic potential energy function. The individual N H…O=C, C H…O=C, C H…N attractive interactions are about 5.3±1.8, 1.2±0.4, and 0.8 kcal/mol, respectively, the individual N H … N could be as strong as about 8.1 kcal/mol or as weak as 1.0 kcal/mol, while the individual C=O…O=C, N H…H N, C H…H N, and C H…H C repulsive interactions are about 1.8±1.1, 1.7±0.6, 0.6±0.3, and 0.35±0.15 kcal/mol. These data are helpful for the rational design of new strategies for molecular recognition or supramolecular assemblies.展开更多
A peptide nucleic acid （PNA）-peptide conjugated molecule, T＇3（AKAE）2, was designed to have both a PNA segment for oligo- nucleotide binding and an ionic self-complementary peptide sequence for self-association. T...A peptide nucleic acid （PNA）-peptide conjugated molecule, T＇3（AKAE）2, was designed to have both a PNA segment for oligo- nucleotide binding and an ionic self-complementary peptide sequence for self-association. T＇3（AKAE）2 could co-assemble with oligoadenines （d（A）x） to form virus-like supramolecular structures whose morphology showed dependence on the chain length and rigidity of the d（A）x molecules. Smaller nanospheres with diameters of 13.0±2.0 nm were produced in the case of d（A）6. Wormlike aggregates with lengths of 20-50 nm and diameters of 15.0±2.5 nm were found in the cases of d（A）12, d（A）ls, d（A）24 and d（A）30. And larger spherical aggregates with diameters of 18±5 nm came into presence in the cases of d（A）36 and d（A）42＋. These nanostructures were suggested to be formed under a cooperative effect of base pair recognition and peptidic association. The study provides insights into the programmed assembly of a multi-components system as well as control of the size and shade of the co-assembled structures, which is of great significance in develouing gene/drug deliverv systems.展开更多
基金supported by the National Natural Science Foundation of China(20825206,20091350914 & 90913003)the Specialized Research Fund for the Doctoral Program of Higher Education (20100002110069)
文摘Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydrophobic interaction between the ligand(ThT) and substrate(Aβ1-42) are stronger than hydrogen bonds.Furthermore,ThT tends to be located near the C-terminus of Aβ monomer through hydrophobic and electrostatic interactions,while it tends to contact the residues Met35 and Gly27 of the fibril surface mainly through hydrophobic interaction.Finally,according to the docking results and ThT fluorescence assay,a kinetic equation is proposed to deduce the aggregation rate coefficient of Aβ1-42.
基金supported by the National Natural Science Foundation of China(21373270,21033005)the Natural Science Foundation of Shandong Province(JQ201105).the support of the Program for New Century Excellent Talents in University(NCET-11-0735)
文摘Numerous peptides derived from naturally occurring proteins or de novo designed have been found to self-assemble into various nanostructures.These well-defined nanostructures have shown great potential for a variety of biomedical and biotechnological applications.In particular,surfactant-like peptides(SLPs)have distinctive advantages in their length,aggregating ability,and water solubility.In this article,we report recent advances in the mechanistic understanding of the self-assembly principles of SLPs and in their applications,most of which have been made in our laboratory.Hydrogen bonding between peptide backbones,hydrophobic interaction between hydrophobic side chains,and electrostatic repulsion between charged head groups all have roles in mediating the self-assembly of SLPs;the final self-assembled nanostructures are therefore dependent on their interplay.SLPs have shown diverse applications ranging from membrane protein stabilization and antimicrobial/anticancer agents to nanofabrication and biomineralization.Future advances in the self-assembly of SLPs will hinge on their large-scale production,the design of new functional SLPs with targeted properties,and the exploitation of new or improved applications.
基金supported by the National Natural Science Foundation of China (21434008, 51503115, 51722302)Qingdao Innovation Leading Talents Program (3rd)
文摘Smart peptide hydrogels are of great interest for their great potential applications. Here, we report a facile approach to prepare a class of enzyme-responsive hydrogels in a scalable manner. These hydrogels self-assemble from a family of nonionic peptide amphiphiles(PAs) synthesized by sequential ring-opening polymerization(ROP) of γ-benzyl-L-glutamate N-carboxyanhydride(BLG-NCA) and L-tyrosine N-carboxyanhydride(Tyr-NCA), followed by subsequent aminolysis. These PA samples can readily form a clear hydrogel with a critical gelation concentration as low as 0.5 wt%. The incorporation of tyrosine residues offers hydrophobicity, hydrogen-bonding interaction and enzyme-responsive properties. The hydrogel-to-nanogel transition is observed under physiological conditions in the presence of horseradish peroxidase(HRP) and hydrogen peroxide(H2 O2). The obtained PA hydrogels are ideal candidates for the new generation of smart scaffolds.
基金Seed Fund of Peking University(Grant No.BMU2018MC003)Peking University Health Science Center(Grant No.BMU20160566)+1 种基金the National Key Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China(Grant No.2016YFA0501203)the National Natural Science Foundation of China(Grant No.31470727,21874004)
文摘Peptide-membrane binding is vital for many biological events,including the bacteria combating by antimicrobial peptides.Using the p H sensitive LAH4 peptide as model,we employed a convenient electron paramagnetic resonance(EPR)method to study the peptide-membrane binding process in artificial phospholipid membranes.Based on spectral changes of the nitroxide radical labeled to the peptides,we characterized binding kinetics and affinity of peptides to different phospholipid membranes.The binding affinity of LAH4 towards POPG was more than an order of magnitude higher than those towards DMPC and POPC.The binding kinetics showed that LAH4 initially bound to POPG much more quickly than to DMPC and POPC.Additionally,p H also affected the binding kinetics in LAH4-membrane interactions,which helped explain the p H dependent antimicrobial activity of LAH4.The method might be further used to monitor the membrane binding/cell penetration of antimicrobial peptide in living cells.
基金supported by the National Natural Science Foundation of China(20973088,21173109,21133005)the Specialized Research Fund for the Doctoral Program of Higher Education(20102136110001)
文摘The binding energies of thirty-six hydrogen-bonded peptide-base complexes, including the peptide backbone-ase complexes and amino acid side chain-base complexes, are evaluated using the analytic potential energy function established in our lab recently and compared with those obtained from MP2, AMBER99, OPLSAA/L, and CHARMM27 calculations. The comparison indicates that the analytic potential energy function yields the binding energies for these complexes as reasonable as MP2 does, much better than the force fields do. The individual N H…O=C, N H…N, C H…O=C, and C H…N attractive interaction energies and C=O…O=C, N H…H N, C H…H N, and C H…H C repulsive interaction energies, which cannot be easily obtained from ab initio calculations, are calculated using the dipole-dipole interaction term of the analytic potential energy function. The individual N H…O=C, C H…O=C, C H…N attractive interactions are about 5.3±1.8, 1.2±0.4, and 0.8 kcal/mol, respectively, the individual N H … N could be as strong as about 8.1 kcal/mol or as weak as 1.0 kcal/mol, while the individual C=O…O=C, N H…H N, C H…H N, and C H…H C repulsive interactions are about 1.8±1.1, 1.7±0.6, 0.6±0.3, and 0.35±0.15 kcal/mol. These data are helpful for the rational design of new strategies for molecular recognition or supramolecular assemblies.
基金the National Natural Science Foundation of China (21473255, 21003160)the Fundamental Research Funds for the Central Universities (14CX05040A, 15CX05017A)
文摘A peptide nucleic acid （PNA）-peptide conjugated molecule, T＇3（AKAE）2, was designed to have both a PNA segment for oligo- nucleotide binding and an ionic self-complementary peptide sequence for self-association. T＇3（AKAE）2 could co-assemble with oligoadenines （d（A）x） to form virus-like supramolecular structures whose morphology showed dependence on the chain length and rigidity of the d（A）x molecules. Smaller nanospheres with diameters of 13.0±2.0 nm were produced in the case of d（A）6. Wormlike aggregates with lengths of 20-50 nm and diameters of 15.0±2.5 nm were found in the cases of d（A）12, d（A）ls, d（A）24 and d（A）30. And larger spherical aggregates with diameters of 18±5 nm came into presence in the cases of d（A）36 and d（A）42＋. These nanostructures were suggested to be formed under a cooperative effect of base pair recognition and peptidic association. The study provides insights into the programmed assembly of a multi-components system as well as control of the size and shade of the co-assembled structures, which is of great significance in develouing gene/drug deliverv systems.
