The main protease(M^(pro))is essential for the replication of SARS-COV-2 and therefore represents a promising anti-viral target.In this study,we screened M^(pro)inhibitory peptides from Ulva prolifera protein on in-si...The main protease(M^(pro))is essential for the replication of SARS-COV-2 and therefore represents a promising anti-viral target.In this study,we screened M^(pro)inhibitory peptides from Ulva prolifera protein on in-silico proteolysis.Cytotoxicity analysis using the online toxic prediction tool ToxinPred revealed that all the peptides were non-cytotoxic.The hexapeptide(SSGFID)exhibited high M^(pro)inhibitory activity in molecular docking and its IC_(50)value was 139.40±0.82μmol/L in vitro according to fluorescence resonance energy transfer assay(FRET).Quantitative real-time(qRT-)PCR results show that SSGFID could stimulate the expression of mitosis-related factors,including nuclear factor-κB,cyclin D1,and cyclin-dependent kinase 4,to promote the proliferation of mice splenocytes.Stability study revealed that SSGFID showed resistance against pepsin and trypsin but lost D(Asp)after pretreatment at121℃ for 15 min.Besides,SSGFID was mainly transported through the Caco-2 cell monolayer by the peptide transporter PepT1 and passive-mediated transport during the transport study.Unfortunately,the peptide was also degraded by Caco-2 intracellular enzymes,and the transfer rate of intact peptide was4.2%.Furthermore,Lineweaver–Burk plots demonstrated that SSGFID possessed a mixed inhibitory characteristic with M^(pro).Our study indicated the potential of Ulva prolifera as antiviral and immuneenhancing functional food ingredients and nutraceuticals.展开更多
AIM: To determine available information on an independent peptide transporter 1(Pep T1) and its potential relevance to treatment, this evaluation was completed.METHODS: Fully published English language literature arti...AIM: To determine available information on an independent peptide transporter 1(Pep T1) and its potential relevance to treatment, this evaluation was completed.METHODS: Fully published English language literature articles sourced through Pub Med related to protein digestion and absorption, specifically human peptide and amino acid transport, were accessed and reviewed.Papers from 1970 to the present, with particular emphasis on the past decade, were examined. In addition,abstracted information translated to English in Pub Med was also included. Finally, studies and reviews relevant to nutrient or drug uptake, particularly in human intestine were included for evaluation. This work represents a summary of all of these studies with particular reference to peptide transporter mediated assimilation of nutrients and pharmacologically active medications.RESULTS: Assimilation of dietary protein in humans involves gastric and pancreatic enzyme hydrolysis to luminal oligopeptides and free amino acids. During the ensuing intestinal phase, these hydrolytic products are transported into the epithelial cell and, eventually, the portal vein. A critical component of this process is the uptake of intact di-peptides and tri-peptides by an independent Pep T1. A number of "peptide-mimetic" pharmaceutical agents may also be transported through this carrier, important for uptake of different antibiotics, antiviral agents and angiotensin-converting enzyme inhibitors. In addition, specific peptide products of intestinal bacteria may also be transported by Pep T1, with initiation and persistence of an immune response including increased cytokine production and associated intestinal inflammatory changes. Interestingly, these inflammatory changes may also be attenuated with orallyadministered anti-inflammatory tripeptides administered as site-specific nanoparticles and taken up by this Pep T1 transport protein. CONCLUSION: Further evaluation of the role of this transporter in treatment of intestinal disorders, including inflammatory bowel 展开更多
The transporter associated with antigen processing （TAP） belongs to the ATP-binding cassette （ABC） transporter superfamily. Driven by ATP hydrolysis, TAP translocates antigenic peptides from the cytosol into the ...The transporter associated with antigen processing （TAP） belongs to the ATP-binding cassette （ABC） transporter superfamily. Driven by ATP hydrolysis, TAP translocates antigenic peptides from the cytosol into the ER （endoplasmic reticulum） lumen where the antigenic peptides are loaded onto the HLA class I molecules. Recently, numerous studies show that TAP is closely related with various diseases such as viral infections, autoimmune diseases, and different malignancies. In consideration of important roles of TAP in human adaptive immunity, this review summarizes the recent advances in structure-function relationships of crucial domains and transport mechanism systematically. The challenging problems and potential methods are also pointed out for in-depth researches.展开更多
The formation of alkali and alkaline-earth metal picrate complexes with cyclo(Pro-Gly)n ionophores (1, n = 3; 2, n = 4) can facilitate the migration of metal ions across a bulk liquid CH2Cl2 membrane. The migration be...The formation of alkali and alkaline-earth metal picrate complexes with cyclo(Pro-Gly)n ionophores (1, n = 3; 2, n = 4) can facilitate the migration of metal ions across a bulk liquid CH2Cl2 membrane. The migration behavior was studied by measuring the solution absorption at 356 nm, using a UV/Vis spectrophotometer, and the rates can be determined by comparing the initial absorption of donor solutions with the absorption of the corresponding receiver solutions as the function of time. It was found that cyclic peptide 1 shows higher transport activity for the studied alkali and alkaline-earth metal ions than compound 2, which is related to the backbone flexibility of the cyclic peptides. The findings in this work suggest that the rate of ionophore-facilitated ion transport depends not only on the ability of complex formation in aqueous phase, but also on the ability of complex dissociation in organic phase.展开更多
Amyotrophic lateral sclerosis is the most common adult-onset neurodegenerative disease affecting motor neurons. Its defining feature is progressive loss of motor neuron function in the cortex, brainstem, and spinal co...Amyotrophic lateral sclerosis is the most common adult-onset neurodegenerative disease affecting motor neurons. Its defining feature is progressive loss of motor neuron function in the cortex, brainstem, and spinal cord, leading to paralysis and death. Despite major advances in identifying genes that can cause disease when mutated and model the disease in animals and cellular models, it still remains unclear why motor symptoms suddenly appear after a long pre-symptomatic phase of apparently normal function. One hypothesis is that age-related deregulation of specific proteins within key cell types, especially motor neurons themselves, initiates disease symptom appearance and may also drive progressive degeneration. Genome-wide in vivo cell-type-specific screening tools are enabling identification of candidates for such proteins. In this minireview, we first briefly discuss the methodology used in a recent study that applied a motor neuron-specific RNASeq screening approach to a standard model of TAR DNA-binding protein-43(TDP-43)-driven amyotrophic lateral sclerosis. A key finding of this study is that synaptogyrin-4 and pleckstrin homology domain-containing family B member 1 are also deregulated at the protein level within motor neurons of two unrelated mouse models of mutant TDP-43 driven amyotrophic lateral sclerosis. Guided by what is known about molecular and cellular functions of these proteins and their orthologs, we outline here specific hypotheses for how changes in their levels might potentially alter cellular physiology of motor neurons and detrimentally affect motor neuron function. Where possible, we also discuss how this information could potentially be used in a translational context to develop new therapeutic strategies for this currently incurable, devastating disease.展开更多
Dietary di/tripeptides elicit preventive effects against lifestyle-related diseases such as hypertension,and hypercholesterolemia,etc.Although there have been evidential reports that the intake of protein hydrolysate ...Dietary di/tripeptides elicit preventive effects against lifestyle-related diseases such as hypertension,and hypercholesterolemia,etc.Although there have been evidential reports that the intake of protein hydrolysate improved impaired memory in human,limited studies on bioavailability,in particular,beyond the blood-brain barrier(BBB)of candidates in hydrolysate may prevent their extensive physiological studies.Thus,this review discusses the updated studies on BBB transport of peptides showing improved cognitive decline.Furthermore,their accumulation in the brain cerebral parenchyma is also introduced.展开更多
Characterization of conformation kinetics of proteins at the interfaces is crucial for understanding the biornolecular functions and the mechanisms of interfacial biological action. But it requires to capture the dyna...Characterization of conformation kinetics of proteins at the interfaces is crucial for understanding the biornolecular functions and the mechanisms of interfacial biological action. But it requires to capture the dynamic structures of proteins at the interfaces with suffi- cient structural and temporal resolutions. Here, we demonstrate that a ferntosecond sum frequency generation vibrational spectroscopy （SFG-VS） system developed by our group provides a powerful tool for monitoring the real-tirne peptide transport across the membranes with time resolution of less than one second. By probing the real-time SFG signals in the arnide I and arnide A bands as WALP23 interacts with DMPG lipid bilayer, it is found that WALP23 is initially absorbed at the gel-phase DMPG bilayer with a random coil structure. The absorption of WALP23 on the surface leads to the surface charge reversal and thus changes the orientation of rnembrane-bound water. As the DMPG bilayer changes from gel phase into fluid phase, WALP23 inserts into the fluid-phase bilayer with its N-terminal end moving across the membrane, which causes the membrane dehydration and the transition of WALP23 conformation from random coil to mixed helix/loop structure and then to pure α-helical structure. The established system is ready to be employed in characterizing other interracial fast processes, which will be certainly helpful for providing a clear physical picture of the interracial phenomena.展开更多
基金Supported by the National Key R&D Program of China (No.2016YFC1402102)the National Natural Science Foundation of China (No.41976109)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)。
文摘The main protease(M^(pro))is essential for the replication of SARS-COV-2 and therefore represents a promising anti-viral target.In this study,we screened M^(pro)inhibitory peptides from Ulva prolifera protein on in-silico proteolysis.Cytotoxicity analysis using the online toxic prediction tool ToxinPred revealed that all the peptides were non-cytotoxic.The hexapeptide(SSGFID)exhibited high M^(pro)inhibitory activity in molecular docking and its IC_(50)value was 139.40±0.82μmol/L in vitro according to fluorescence resonance energy transfer assay(FRET).Quantitative real-time(qRT-)PCR results show that SSGFID could stimulate the expression of mitosis-related factors,including nuclear factor-κB,cyclin D1,and cyclin-dependent kinase 4,to promote the proliferation of mice splenocytes.Stability study revealed that SSGFID showed resistance against pepsin and trypsin but lost D(Asp)after pretreatment at121℃ for 15 min.Besides,SSGFID was mainly transported through the Caco-2 cell monolayer by the peptide transporter PepT1 and passive-mediated transport during the transport study.Unfortunately,the peptide was also degraded by Caco-2 intracellular enzymes,and the transfer rate of intact peptide was4.2%.Furthermore,Lineweaver–Burk plots demonstrated that SSGFID possessed a mixed inhibitory characteristic with M^(pro).Our study indicated the potential of Ulva prolifera as antiviral and immuneenhancing functional food ingredients and nutraceuticals.
文摘AIM: To determine available information on an independent peptide transporter 1(Pep T1) and its potential relevance to treatment, this evaluation was completed.METHODS: Fully published English language literature articles sourced through Pub Med related to protein digestion and absorption, specifically human peptide and amino acid transport, were accessed and reviewed.Papers from 1970 to the present, with particular emphasis on the past decade, were examined. In addition,abstracted information translated to English in Pub Med was also included. Finally, studies and reviews relevant to nutrient or drug uptake, particularly in human intestine were included for evaluation. This work represents a summary of all of these studies with particular reference to peptide transporter mediated assimilation of nutrients and pharmacologically active medications.RESULTS: Assimilation of dietary protein in humans involves gastric and pancreatic enzyme hydrolysis to luminal oligopeptides and free amino acids. During the ensuing intestinal phase, these hydrolytic products are transported into the epithelial cell and, eventually, the portal vein. A critical component of this process is the uptake of intact di-peptides and tri-peptides by an independent Pep T1. A number of "peptide-mimetic" pharmaceutical agents may also be transported through this carrier, important for uptake of different antibiotics, antiviral agents and angiotensin-converting enzyme inhibitors. In addition, specific peptide products of intestinal bacteria may also be transported by Pep T1, with initiation and persistence of an immune response including increased cytokine production and associated intestinal inflammatory changes. Interestingly, these inflammatory changes may also be attenuated with orallyadministered anti-inflammatory tripeptides administered as site-specific nanoparticles and taken up by this Pep T1 transport protein. CONCLUSION: Further evaluation of the role of this transporter in treatment of intestinal disorders, including inflammatory bowel
基金Supported by Programme of Introducing Talents of Discipline to Universities(‘111’project)the Key Natural Science Foundation of Chongqing(CSTC,2009BA5068)the Fundamental Research Funds for the Central Universities(CDJXS,11231177)
文摘The transporter associated with antigen processing （TAP） belongs to the ATP-binding cassette （ABC） transporter superfamily. Driven by ATP hydrolysis, TAP translocates antigenic peptides from the cytosol into the ER （endoplasmic reticulum） lumen where the antigenic peptides are loaded onto the HLA class I molecules. Recently, numerous studies show that TAP is closely related with various diseases such as viral infections, autoimmune diseases, and different malignancies. In consideration of important roles of TAP in human adaptive immunity, this review summarizes the recent advances in structure-function relationships of crucial domains and transport mechanism systematically. The challenging problems and potential methods are also pointed out for in-depth researches.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 29872021).
文摘The formation of alkali and alkaline-earth metal picrate complexes with cyclo(Pro-Gly)n ionophores (1, n = 3; 2, n = 4) can facilitate the migration of metal ions across a bulk liquid CH2Cl2 membrane. The migration behavior was studied by measuring the solution absorption at 356 nm, using a UV/Vis spectrophotometer, and the rates can be determined by comparing the initial absorption of donor solutions with the absorption of the corresponding receiver solutions as the function of time. It was found that cyclic peptide 1 shows higher transport activity for the studied alkali and alkaline-earth metal ions than compound 2, which is related to the backbone flexibility of the cyclic peptides. The findings in this work suggest that the rate of ionophore-facilitated ion transport depends not only on the ability of complex formation in aqueous phase, but also on the ability of complex dissociation in organic phase.
基金supported in part by funding from the Else Kr?ner Fresenius Stiftung(Co-PI)the Werner Otto Stiftung(PI)(to KED)。
文摘Amyotrophic lateral sclerosis is the most common adult-onset neurodegenerative disease affecting motor neurons. Its defining feature is progressive loss of motor neuron function in the cortex, brainstem, and spinal cord, leading to paralysis and death. Despite major advances in identifying genes that can cause disease when mutated and model the disease in animals and cellular models, it still remains unclear why motor symptoms suddenly appear after a long pre-symptomatic phase of apparently normal function. One hypothesis is that age-related deregulation of specific proteins within key cell types, especially motor neurons themselves, initiates disease symptom appearance and may also drive progressive degeneration. Genome-wide in vivo cell-type-specific screening tools are enabling identification of candidates for such proteins. In this minireview, we first briefly discuss the methodology used in a recent study that applied a motor neuron-specific RNASeq screening approach to a standard model of TAR DNA-binding protein-43(TDP-43)-driven amyotrophic lateral sclerosis. A key finding of this study is that synaptogyrin-4 and pleckstrin homology domain-containing family B member 1 are also deregulated at the protein level within motor neurons of two unrelated mouse models of mutant TDP-43 driven amyotrophic lateral sclerosis. Guided by what is known about molecular and cellular functions of these proteins and their orthologs, we outline here specific hypotheses for how changes in their levels might potentially alter cellular physiology of motor neurons and detrimentally affect motor neuron function. Where possible, we also discuss how this information could potentially be used in a translational context to develop new therapeutic strategies for this currently incurable, devastating disease.
文摘Dietary di/tripeptides elicit preventive effects against lifestyle-related diseases such as hypertension,and hypercholesterolemia,etc.Although there have been evidential reports that the intake of protein hydrolysate improved impaired memory in human,limited studies on bioavailability,in particular,beyond the blood-brain barrier(BBB)of candidates in hydrolysate may prevent their extensive physiological studies.Thus,this review discusses the updated studies on BBB transport of peptides showing improved cognitive decline.Furthermore,their accumulation in the brain cerebral parenchyma is also introduced.
基金supported by the National Natural Science Foundation of China(No.21473177,No.21633007)the National Key Research and Development Program of China(No.2017YFA0303500 and No.2018YFA0208700)+1 种基金Fundamental Research Funds for the Central Universities(No.WK2340000064)Anhui Initiative in Quantum Information Technologies(No.AHY090000)
文摘Characterization of conformation kinetics of proteins at the interfaces is crucial for understanding the biornolecular functions and the mechanisms of interfacial biological action. But it requires to capture the dynamic structures of proteins at the interfaces with suffi- cient structural and temporal resolutions. Here, we demonstrate that a ferntosecond sum frequency generation vibrational spectroscopy （SFG-VS） system developed by our group provides a powerful tool for monitoring the real-tirne peptide transport across the membranes with time resolution of less than one second. By probing the real-time SFG signals in the arnide I and arnide A bands as WALP23 interacts with DMPG lipid bilayer, it is found that WALP23 is initially absorbed at the gel-phase DMPG bilayer with a random coil structure. The absorption of WALP23 on the surface leads to the surface charge reversal and thus changes the orientation of rnembrane-bound water. As the DMPG bilayer changes from gel phase into fluid phase, WALP23 inserts into the fluid-phase bilayer with its N-terminal end moving across the membrane, which causes the membrane dehydration and the transition of WALP23 conformation from random coil to mixed helix/loop structure and then to pure α-helical structure. The established system is ready to be employed in characterizing other interracial fast processes, which will be certainly helpful for providing a clear physical picture of the interracial phenomena.
