Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cyt...Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cytokines are essential mediators between activated immune and non-immune cells, including epithelial and mes- enchymal cells. They are immunomodulatory peptides released by numerous cells and these have significant effects on immune function leading to the differentiation and survival of T cells. The physiology of IBD is becom- ing a very attractive field of research for development of new therapeutic agents. These include cytokines involved in intestinal immune inflammation. This review will focus on mechanisms of action of oytokines involved in IBD and new therapeutic opportunities for these diseases.展开更多
Cyclotides constitute a fascinating family of circular proteins containing ca.30 amino acid residues.They have a unique cyclic cysteine knot topology and exhibit remarkable thermal,chemical and enzymatic stabilities.T...Cyclotides constitute a fascinating family of circular proteins containing ca.30 amino acid residues.They have a unique cyclic cysteine knot topology and exhibit remarkable thermal,chemical and enzymatic stabilities.These characteristics enable them to have a range of biological activities and promising pharmaceutical and agricultural applications.Here,we present a practical strategy for the chemical synthesis of cyclotides through the intramolecular ligation of fully unprotected peptide O-esters.This strategy involves the mild Fmoc solid-phase peptide synthesis of the peptide O-ester backbone,the head-to-tail cyclization of the cyclotide backbone by native chemical ligation,and the oxidative refolding to yield the natural knot protein.The simplicity and high efficiency of the strategy can be employed in the synthesis of artificial cyclotides for pharmaceutical applications.展开更多
Chemical examination of an unidentified sponge associated marine fungus Penicillium terrestre resulted in the isolation of eight compounds. Their structures are identified as cyclo （glycyl-D-proline） （1）, cyclo （...Chemical examination of an unidentified sponge associated marine fungus Penicillium terrestre resulted in the isolation of eight compounds. Their structures are identified as cyclo （glycyl-D-proline） （1）, cyclo （L-prolyl-L-alanine） （2）, cyclo （L-prolyl- D-alanine） （3）, cyclo （L-leucyl-trans-4-hydroxy-L-proline） （4）, cyclo （L-leucyl-cis-4-hydroxy-D-proline） （5）, cyclo （L-trans-（4- hydroxyprolinyl）-L-phenylalanine） （6）, hexylitaconic acid （7）, and hexylitaconic methylate （8）, based on spectroscopic analysis （1D, 2D NMR）. Compounds 7, 8 were obtained from the genus Penicillium for the first time, while compounds 1-6 were isolated from the fungus Penicillium terrestre for the first time.展开更多
Elevated CO 2 may reduce the tolerance of Nilaparvata lugen (N. lugens) to adverse environmental factors through the biological and physiological degeneration of N. lugens. In an artificial climate box, under 375 and ...Elevated CO 2 may reduce the tolerance of Nilaparvata lugen (N. lugens) to adverse environmental factors through the biological and physiological degeneration of N. lugens. In an artificial climate box, under 375 and 750 μL L 1 CO 2 levels, the rice stems nutrient content, the nutrient content and enzyme activities of N. lugens nymph fed on rice seedlings exposed to ambient and elevated CO 2 were studied. The results showed that rice stems had significantly higher protein and total amino acid levels under ambient than elevated CO 2 levels. Nymphs had significantly higher protein levels in the ambient CO 2 treatment, while their glucose levels were significantly lower under ambient CO 2 conditions. Significantly higher trypsin activity was observed in nymphs grown in elevated CO 2 . Significantly lower activities of the protective enzymes total superoxide dismutase and catalase were observed in the nymphs under ambient CO 2 . Meanwhile, the activity of the detoxification enzyme glutathione S-transferase was significantly higher in the ambient CO 2 treatment. Measuring how energy and resources were allocated to enzymes in N. lugens nymphs under elevated CO 2 conditions can provide a more meaningful evaluation of their metabolic tolerances to adverse climatic conditions.展开更多
Peptides/proteins aggregation can give rise to pathological conditions of many human diseases.Small partially ordered oligomers formed in the early stage of aggregation,rather than mature fibrils,are thought to be the...Peptides/proteins aggregation can give rise to pathological conditions of many human diseases.Small partially ordered oligomers formed in the early stage of aggregation,rather than mature fibrils,are thought to be the main toxicity agent for the living cell.Thus,understanding the pathway and the underlying physical mechanism in the early stage of aggregation is very important for prevention and treatment of these protein functional diseases.Herein we use all-atom molecular dynamics simulations to study the aggregation of four NFGAIL hexapeptides(NFGAIL peptide is a core segment of human islet amyloid polypeptide and exhibits similar aggregation kinetics as the full-length polypeptide).We observe that the peptide monomers in water mainly adopt non-structural coil configurations;the four peptides which are randomly placed in water aggregate spontaneously to partially ordered oligomer(β-sheets)through dimerization or trimerization,with the dimerization predominated.Both parallel and anti-parallelβ-sheets are observed.The hydrophobic interactions drive the initial peptides associations,and the subsequent conformational fluctuations promote the formation of more hydrogen bonds between the dangling hydrogen sites in the main chains of peptides.展开更多
文摘Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cytokines are essential mediators between activated immune and non-immune cells, including epithelial and mes- enchymal cells. They are immunomodulatory peptides released by numerous cells and these have significant effects on immune function leading to the differentiation and survival of T cells. The physiology of IBD is becom- ing a very attractive field of research for development of new therapeutic agents. These include cytokines involved in intestinal immune inflammation. This review will focus on mechanisms of action of oytokines involved in IBD and new therapeutic opportunities for these diseases.
基金supported by the National Natural Science Foundation of China(20932006,91013007)the National Basic Research Program of China(973 Program)(2011CB965300)
文摘Cyclotides constitute a fascinating family of circular proteins containing ca.30 amino acid residues.They have a unique cyclic cysteine knot topology and exhibit remarkable thermal,chemical and enzymatic stabilities.These characteristics enable them to have a range of biological activities and promising pharmaceutical and agricultural applications.Here,we present a practical strategy for the chemical synthesis of cyclotides through the intramolecular ligation of fully unprotected peptide O-esters.This strategy involves the mild Fmoc solid-phase peptide synthesis of the peptide O-ester backbone,the head-to-tail cyclization of the cyclotide backbone by native chemical ligation,and the oxidative refolding to yield the natural knot protein.The simplicity and high efficiency of the strategy can be employed in the synthesis of artificial cyclotides for pharmaceutical applications.
基金National 863 Projects(Grant No.2007AA09Z448 and 2008AA09Z405)
文摘Chemical examination of an unidentified sponge associated marine fungus Penicillium terrestre resulted in the isolation of eight compounds. Their structures are identified as cyclo （glycyl-D-proline） （1）, cyclo （L-prolyl-L-alanine） （2）, cyclo （L-prolyl- D-alanine） （3）, cyclo （L-leucyl-trans-4-hydroxy-L-proline） （4）, cyclo （L-leucyl-cis-4-hydroxy-D-proline） （5）, cyclo （L-trans-（4- hydroxyprolinyl）-L-phenylalanine） （6）, hexylitaconic acid （7）, and hexylitaconic methylate （8）, based on spectroscopic analysis （1D, 2D NMR）. Compounds 7, 8 were obtained from the genus Penicillium for the first time, while compounds 1-6 were isolated from the fungus Penicillium terrestre for the first time.
基金supported by the National Natural Science Foundation of China(Grant Nos.31071691 and 31171846)the Major Projects of Cultivated Varieties of Genetically Modified Organisms(Grant No.2011ZX08012-005)the Self-determined and Innovative Research Funds of Wuhan University of Technology(Grant No.2011-1a-037),China
文摘Elevated CO 2 may reduce the tolerance of Nilaparvata lugen (N. lugens) to adverse environmental factors through the biological and physiological degeneration of N. lugens. In an artificial climate box, under 375 and 750 μL L 1 CO 2 levels, the rice stems nutrient content, the nutrient content and enzyme activities of N. lugens nymph fed on rice seedlings exposed to ambient and elevated CO 2 were studied. The results showed that rice stems had significantly higher protein and total amino acid levels under ambient than elevated CO 2 levels. Nymphs had significantly higher protein levels in the ambient CO 2 treatment, while their glucose levels were significantly lower under ambient CO 2 conditions. Significantly higher trypsin activity was observed in nymphs grown in elevated CO 2 . Significantly lower activities of the protective enzymes total superoxide dismutase and catalase were observed in the nymphs under ambient CO 2 . Meanwhile, the activity of the detoxification enzyme glutathione S-transferase was significantly higher in the ambient CO 2 treatment. Measuring how energy and resources were allocated to enzymes in N. lugens nymphs under elevated CO 2 conditions can provide a more meaningful evaluation of their metabolic tolerances to adverse climatic conditions.
基金Supported by the National Natural Science Foundation of China under Grant Nos.30870593 and 11204269the China Postdoctoral Science Foundation under Grant No.2012M511351+2 种基金Zhejiang Provincial Natural Science Foundation of China under Grant No.LY12A04007the Fundamental Research Funds for the Central Universitiesthe KYLIN-I Supercomputer in Institute for Fusion Theory and Simulation,Zhejiang University
文摘Peptides/proteins aggregation can give rise to pathological conditions of many human diseases.Small partially ordered oligomers formed in the early stage of aggregation,rather than mature fibrils,are thought to be the main toxicity agent for the living cell.Thus,understanding the pathway and the underlying physical mechanism in the early stage of aggregation is very important for prevention and treatment of these protein functional diseases.Herein we use all-atom molecular dynamics simulations to study the aggregation of four NFGAIL hexapeptides(NFGAIL peptide is a core segment of human islet amyloid polypeptide and exhibits similar aggregation kinetics as the full-length polypeptide).We observe that the peptide monomers in water mainly adopt non-structural coil configurations;the four peptides which are randomly placed in water aggregate spontaneously to partially ordered oligomer(β-sheets)through dimerization or trimerization,with the dimerization predominated.Both parallel and anti-parallelβ-sheets are observed.The hydrophobic interactions drive the initial peptides associations,and the subsequent conformational fluctuations promote the formation of more hydrogen bonds between the dangling hydrogen sites in the main chains of peptides.
