caa a22 4500 445326549 CHVBK 20180317142722.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10989-011-9273-9 doi (NATIONALLICENCE)springer-10.1007/s10989-011-9273-9 Improving the Fmoc Solid Phase Synthesis of the Cyclic Hexapeptide Complement C5a Antagonist, PMX205 [Elektronische Daten] [R. deLisle Milton, S. Milton, A. Chamberlin] The anti-inflammatory drug, PMX205, is an antagonist of the C5a complement receptor and has been shown to be effective in rodent models of amyotrophic lateral sclerosis and Alzheimer's disease. This cyclic hexapeptide (c[Arg-Trp-D-Cha-Pro-Orn]-Hca) has been reported to produce relatively low yields for both the linear peptide assembly and the cyclization reaction in solution and solid phase syntheses. During attempts to reproduce the solid phase methodology, a catastrophic loss of substitution was encountered which could be avoided or reduced by the use of 2-chlorotrityl resin. Likewise, the cyclization reaction could be significantly improved by the use of FDPP (pentafluorophenyl diphenylphosphinate) at high dilution (up to 80% purified yield). Both improvements are accomplished with commercially available products. Springer Science+Business Media, LLC, 2011 PMX205 nationallicence C5a antagonist nationallicence Cyclic peptide nationallicence Fmoc solid phase synthesis nationallicence Optimization nationallicence Boc : tert-Butyloxycarbonyl nationallicence COMU : 4-[[[(1-cyano-2-ethoxy-2-oxoethylidene)amino] oxayl](dimethylamino)methylene]morpholinium hexafluorophosphate nationallicence DBU : 1,8-diazabicyclo[5.4.0]undec-7-ene nationallicence D-Cha : D-cyclohexylalanine nationallicence DEAE : Diethylaminoethyl nationallicence Dde : N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl) nationallicence DIPC : Diisopropylcarbodiimide nationallicence DIPEA : N,N-diisopropylethylamine nationallicence DMF : Dimethylformamide nationallicence ESI-MS : Electrospray ionization mass spectroscopy nationallicence FDPP : Pentafluorophenyl diphenylphosphinate nationallicence Fmoc : 9-fluorenylmethyloxycarbonyl nationallicence fw : Formula weight nationallicence GC-MS : Gas chromatography mass spectrometry nationallicence HATU : N-[(dimethylamino)-1H-1,2,2-triazolo[4,5-b]pyridine-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate nationallicence Hca : Hydrocinnaminic acid nationallicence HOAt : 1-hydroxy-7-azabenzotriazole nationallicence MTBE : Methyl tert-butyl ether nationallicence mw : Molecular weight nationallicence Pbf : 2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-sulfonyl nationallicence PyBOP : Benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate nationallicence RP-HPLC : Reversed phase high performance liquid chromatography nationallicence TFA : Trifluoroacetic acid nationallicence deLisle Milton R. Department of Pharmaceutical Sciences, University of California at Irvine, 92697, Irvine, CA, USA aut Milton S. Department of Molecular Biology and Biochemistry, University of California at Irvine, 92697, Irvine, CA, USA aut Chamberlin A. Department of Pharmaceutical Sciences, University of California at Irvine, 92697, Irvine, CA, USA aut International Journal of Peptide Research and Therapeutics Springer Netherlands 17/4(2011-12-01), 337-342 1573-3149 17:4<337 2011 17 10989 https://doi.org/10.1007/s10989-011-9273-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10989-011-9273-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- deLisle Milton R. Department of Pharmaceutical Sciences, University of California at Irvine, 92697, Irvine, CA, USA aut NATIONALLICENCE 700 1- Milton S. Department of Molecular Biology and Biochemistry, University of California at Irvine, 92697, Irvine, CA, USA aut NATIONALLICENCE 700 1- Chamberlin A. Department of Pharmaceutical Sciences, University of California at Irvine, 92697, Irvine, CA, USA aut NATIONALLICENCE 773 0- International Journal of Peptide Research and Therapeutics Springer Netherlands 17/4(2011-12-01), 337-342 1573-3149 17:4<337 2011 17 10989 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer