Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the μ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisati...Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the μ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisation through the formation of a disulfide bridge between the side chains of cysteine residues added to the sequence was explored. A further increase in stability was achieved through N-terminal modification with lipoamino acid and lactose succinamic acid, and the inclusion of D-amino acids. The latter also provided an alternative spatial arrangement of the aromatic side chains. The lipidated cyclic derivatives were insoluble in aqueous buffer, however, the cyclic peptides and glycopeptides showed greatly improved stability towards enzymatic degradation in human plasma.展开更多
Several ZSM-5 derived micro-mesoporous catalysts were investigated in Prins cyclisation of (-)-isopulegol with benzaldehyde acting as a reactant and a solvent for production of heterocyclic oxygen containing 2H-chrome...Several ZSM-5 derived micro-mesoporous catalysts were investigated in Prins cyclisation of (-)-isopulegol with benzaldehyde acting as a reactant and a solvent for production of heterocyclic oxygen containing 2H-chromene derivatives including the tetrahydropyran structure and exhibiting biological activity. The investigated catalysts were characterized by nitrogen adsorption, ammonia temperature programmed desorption, adsorption-desorption of pyridine and 2,6-di-tert- butylpyridine with Fourier transform infrared spectroscopic control. For the Prins reaction performed at 70℃, the highest yield of the desired product, equal to 67% at complete conversion of (-)-isopulegol, was obtained over a micro-mesoporous catalyst containing an optimum amount of strong acid sites and mesopores, being 12 fold larger than the size of the desired product.展开更多
Ten novel butterfly-shaped dithienobenzosilole-based luminogens,which are peripherally installed with a variety of substituents including hydrogen,phenyl and substituted phenyl groups,have been readily prepared via an...Ten novel butterfly-shaped dithienobenzosilole-based luminogens,which are peripherally installed with a variety of substituents including hydrogen,phenyl and substituted phenyl groups,have been readily prepared via an iodine-induced intramolecular electrophilic double-cyclisation reaction and subsequent deiodination or coupling reactions.The optical and electrochemical properties of these compounds were systematically investigated to clarify the relationships between their structures and properties,supported by theoretical calculations.These compounds exhibit deep-blue to sky-blue emissions and high photoluminescence quantum yields up to 0.84 in solution and solid states which are regulated by the functional blades and their steric hindrance on theα–andβ–positions of thiophene rings.Their high thermal-and photo-stabilities have been revealed and mainly attributed to the dithienobenzosilole core.展开更多
OBJECTIVE Relaxin-3 is a novel neuropeptide of the relaxin insulin family of peptides.So far,many studies have reported the role of relaxin-3/RXFP3 system in regulating feeding,stress response and cognition.In previou...OBJECTIVE Relaxin-3 is a novel neuropeptide of the relaxin insulin family of peptides.So far,many studies have reported the role of relaxin-3/RXFP3 system in regulating feeding,stress response and cognition.In previous studies using RXFP3 stable cell lines,inhibition of adenylate cyclase by the activation of Gi/o proteins have been reported.Based on this signaling event,we have developed inhibition of forskolin induced cAMP assay to detect RXFP3 activation or inhibition by its agonists or antagonists.METHODS To detect inhibition of adenylate cyclase up on RXFP3 activation by human relaxin-3(H3relaxin),HEK-RXFP3,CHO-RXFP3,SN56 and GT1-7cells were plated in poly-L-lysine coated 24 well plates.The following day,the cells were starved in serum free cell culture media for 6h.Next,cells were treated in triplicate with serum free media(control)and H3 relaxin for 5-15 min.Then,the cells were treated with serum free media with DMSO(control)or forskolin(5-100μmol·L-1)for 15 min at 37℃ with 5%CO2.At the end of the incubation,cell culture media was discarded and the cells were lysed with 0.1mol·L-1 HCl.The cAMP concentration in each lysate was detected by ELISA(Cayman Chemicals).The data from three experiments were analysed using one way ANOVA followed by Bonferroni post hoc test or Dunnett′s post hoc test.RESULTS In CHO-RXFP3 and HEK-RXFP3 cells,10nmol·L-1 of H3 relaxin was able to significantly inhibit the forskolin(5μmol·L-1)induced cAMP levels(P<0.05).In SN56 neuronal like cell line endogenously expressing RXFP3,100nmol·L-1 H3 relaxin was able to significantly reduce forskolin(3μmol·L-1)induced cAMP(P<0.05).However,in wild type HEK293 Tand CHO-K1 cells,10n mol·L-1 H3 relaxin was not able to significantly reduce the forskolin 22(5μmol·L-1)induced cAMP levels.In GT1-7 mouse hypothalamic cells endogenously expressing RXFP3,100nmol·L-1 H3 relaxin and 5or 3μmol·L-1 forskolin,was able toa significantly increase cAMP levels(P<0.05).CONCLUSION Inhibition of forskolin induced cAMP assay can be used to detect Gi展开更多
文摘Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the μ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisation through the formation of a disulfide bridge between the side chains of cysteine residues added to the sequence was explored. A further increase in stability was achieved through N-terminal modification with lipoamino acid and lactose succinamic acid, and the inclusion of D-amino acids. The latter also provided an alternative spatial arrangement of the aromatic side chains. The lipidated cyclic derivatives were insoluble in aqueous buffer, however, the cyclic peptides and glycopeptides showed greatly improved stability towards enzymatic degradation in human plasma.
文摘Several ZSM-5 derived micro-mesoporous catalysts were investigated in Prins cyclisation of (-)-isopulegol with benzaldehyde acting as a reactant and a solvent for production of heterocyclic oxygen containing 2H-chromene derivatives including the tetrahydropyran structure and exhibiting biological activity. The investigated catalysts were characterized by nitrogen adsorption, ammonia temperature programmed desorption, adsorption-desorption of pyridine and 2,6-di-tert- butylpyridine with Fourier transform infrared spectroscopic control. For the Prins reaction performed at 70℃, the highest yield of the desired product, equal to 67% at complete conversion of (-)-isopulegol, was obtained over a micro-mesoporous catalyst containing an optimum amount of strong acid sites and mesopores, being 12 fold larger than the size of the desired product.
基金supported by the National Natural Science Foundation of China(No.21501135)。
文摘Ten novel butterfly-shaped dithienobenzosilole-based luminogens,which are peripherally installed with a variety of substituents including hydrogen,phenyl and substituted phenyl groups,have been readily prepared via an iodine-induced intramolecular electrophilic double-cyclisation reaction and subsequent deiodination or coupling reactions.The optical and electrochemical properties of these compounds were systematically investigated to clarify the relationships between their structures and properties,supported by theoretical calculations.These compounds exhibit deep-blue to sky-blue emissions and high photoluminescence quantum yields up to 0.84 in solution and solid states which are regulated by the functional blades and their steric hindrance on theα–andβ–positions of thiophene rings.Their high thermal-and photo-stabilities have been revealed and mainly attributed to the dithienobenzosilole core.
基金The project supported by the Biomedical Research Council of Singapore(BMRC 10/1/21/19/645)National Medical Research Council of Singapore(NMRC/1287/2011)the Ministry of Education,Singapore,Academic Research Fund Tier 1Seed Fund for Basic Science Research(T1-BSRG 2014-03)
文摘OBJECTIVE Relaxin-3 is a novel neuropeptide of the relaxin insulin family of peptides.So far,many studies have reported the role of relaxin-3/RXFP3 system in regulating feeding,stress response and cognition.In previous studies using RXFP3 stable cell lines,inhibition of adenylate cyclase by the activation of Gi/o proteins have been reported.Based on this signaling event,we have developed inhibition of forskolin induced cAMP assay to detect RXFP3 activation or inhibition by its agonists or antagonists.METHODS To detect inhibition of adenylate cyclase up on RXFP3 activation by human relaxin-3(H3relaxin),HEK-RXFP3,CHO-RXFP3,SN56 and GT1-7cells were plated in poly-L-lysine coated 24 well plates.The following day,the cells were starved in serum free cell culture media for 6h.Next,cells were treated in triplicate with serum free media(control)and H3 relaxin for 5-15 min.Then,the cells were treated with serum free media with DMSO(control)or forskolin(5-100μmol·L-1)for 15 min at 37℃ with 5%CO2.At the end of the incubation,cell culture media was discarded and the cells were lysed with 0.1mol·L-1 HCl.The cAMP concentration in each lysate was detected by ELISA(Cayman Chemicals).The data from three experiments were analysed using one way ANOVA followed by Bonferroni post hoc test or Dunnett′s post hoc test.RESULTS In CHO-RXFP3 and HEK-RXFP3 cells,10nmol·L-1 of H3 relaxin was able to significantly inhibit the forskolin(5μmol·L-1)induced cAMP levels(P<0.05).In SN56 neuronal like cell line endogenously expressing RXFP3,100nmol·L-1 H3 relaxin was able to significantly reduce forskolin(3μmol·L-1)induced cAMP(P<0.05).However,in wild type HEK293 Tand CHO-K1 cells,10n mol·L-1 H3 relaxin was not able to significantly reduce the forskolin 22(5μmol·L-1)induced cAMP levels.In GT1-7 mouse hypothalamic cells endogenously expressing RXFP3,100nmol·L-1 H3 relaxin and 5or 3μmol·L-1 forskolin,was able toa significantly increase cAMP levels(P<0.05).CONCLUSION Inhibition of forskolin induced cAMP assay can be used to detect Gi
