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| 1 | Chimeric protein probes for C5a receptors through fusion of the anaphylatoxin C5a core region with a small-molecule antagonist显示文摘Blockade of the interaction of anaphylatoxin C5a with its receptor C5aR1 has been actively studied as a potential treatment for many inflammatory diseases;but current C5a antagonists exhibit inadequate potency and poor species cross-reactivity, and novel biochemical tools are needed to investigate whether the core region of C5a contains important interaction epitopes that can explain these limitations. Herein, we report the development of chimeric protein C5a probes containing both the complete core region of rat or human C5a, and the small-molecule antagonist PMX53-1. These probes were chemically synthesized through hydrazide-based native chemical ligation of a linear peptide hydrazide with the requisite cyclopeptidic antagonist, both of which were made by solid-phase synthesis. Quasi-racemic X-ray crystallography established that attachment of PMX53-1 did not affect the structure of the core region of C5a. Subsequent C5aR1 activity assays demonstrated the probes can provide valuable insights into the development of C5a antagonists;for example, they exhibited significantly better binding affinity and much improved species cross-reactivity than PMX53-1, supporting the notion that the effect of some epitopes outside the C-terminus of C5a should be taken into consideration when designing better C5a antagonists. Surprisingly, the core region of C5a was found to partially agonize C5aR1, suggesting the presence of more than one agonistic interaction in the binding of C5a to C5aR1. This study exemplifies the value of chemical protein synthesis in developing novel receptor probes for drug discovery research. | Chao Zuo Wei-Wei Shi Xiao-Xu Chen Marie Glatz Bernd Riedl Ingo Flamme Elisabeth Pook Jiawei Wang Ge-Min Fang Donald Bierer Lei Liu | 2019 | Science China Chemistry2019，62，10： | 2 |
| 2 | Respiratory detoxification of nitric oxide by the cytochrome c reductase of Escherichia coli 显示文摘 | Pook S Leach R Moir W | 2008 | Journal of Biological Chemistry2008，277，23： | 1 |
| 3 | Variation of live and dead fine fuel moister in Pinus radiata plantations of the Australian capital territory 显示文摘 | Pook E W AM Gill | 1993 | International Journal of Wildland Fire1993，3，3： | 1 |
| 4 | Variation of live and dead fine fuel moister in Pinus radiata plantations of the Australian capital territory 显示文摘 | Pook E W A M Gill | 1993 | International Journal of Wildland Fire1993，3，3： | 1 |
| 5 | Motesanib diphosphate(AMG 706),an oral angiogenesis inhibitor, demonstrates clini-cal efficacy in advanced thymoma 显示文摘 | Azad A Herbertson RA Pook D | 2009 | Acta Oncol2009，48，4： | 1 |
| 6 | Combination of thiol antioxidant Silibinin with Brostallicin is associated with increase in the anti-apoptotic protein Bcl-2 and decrease in caspase 3 activity显示文摘 | SIM-HWEE POOK CHEE-KEONF TOH RATHA MAHENDRAN | 2006 | Cancer Lett2006，238，1： | 1 |
| 7 | Determination of fatigue crack path显示文摘 | Pook L P | 1997 | International Journal of Bifurcation and Chaos1997，7，2： | 1 |
| 8 | Sugar sensing and sugar mediated signal transduction in plants显示文摘 | SMEEKENS S POOK F | 1997 | Plant physiol1997，，115： | 1 |
| 9 | Pneumonia in the surgical patient显示文摘 | Pook HC JR Heinzelmann M Mercer-jones M A | 2004 | Curr Probl Surg2004，34，8： | 1 |
| 10 | Approximate stress intensity factors obtained from simple plate bending theory 显示文摘 | Pook L P | 1979 | Engineering Fracture Mechanics1979，12，4： | 1 |
| 11 | Detection of hypoxia in human squamous cell carcinoma by EF5 binding 显示文摘 | Evans SM Hahn S Pook DR | 2000 | Cancer Res2000，60，7： | 1 |
| 12 | Detection of hypoxia in human squamous cell carcinoma by EF5 binding显示文摘 | Evans SM Hahn S Pook DR | 2000 | Cancer Res2000，60，7： | 1 |
| 13 | Inclusion of nuclear intron sequence data helps to identify the Asian sister group of New World pitvipets 显示文摘 | MALHOTRA A CREER S POOK C E | 2010 | Molecular Phylogenetics and Evolution2010，54，： | 1 |
| 14 | Anestingofvipers: Phylogeny and historical biogeogTaphy of the Viperidae (Squamata:Serpentes) 显示文摘 | WUSTER PEPPIN L POOK C E | 2008 | Molecular Phylogenetics and Evolution2008，19，： | 1 |
| 15 | On fatigue crack paths显示文摘 | POOK L P | 1995 | Journal of Fatigue1995，17，1： | 1 |
| 16 | Ca- and La-substitution in YBa2Cu3O7-δ,Y2Ba4Cu7O15-δ and YBa2Cu4O8显示文摘 | Buckley R G Pooke D M Tallon J L | 1991 | Physica C1991，174，： | 1 |
| 17 | Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3 显示文摘 | Griffin JL Cemal CK Pook MA | 2004 | Physiol Genomics2004，16，3： | 1 |
| 18 | Indian and Pacific Ocean Influences on Southeast Australian Drought and Soil Moisture显示文摘 | Ummenhofer Caroline C Gupta Alexander Sen Briggs Peter R England Matthew H McIntosh Peter C Meyers Gary A Pook Michael J Raupach Michael R Risbey James S | 2011 | Journal of Climate2011，，5： | 1 |
| 19 | Deictic codes for the embodiment of cognition显示文摘 | Ballard D.H Hayhoe M.M Pook P.K Rao R.P.N | | 0，，04： | 1 |
| 20 | Some implications of corner point singularities显示文摘 | Pook L P | 1994 | Engng Fract Mech1994，48，3： | 1 |
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