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pubmed-article:17428094pubmed:abstractTextAminopyrazole derivatives constitute the first class of nonpeptidic rationally designed beta-sheet ligands. Here we describe a double solid-phase protocol for both synthesis and affinity testing. The presented solid-phase synthesis of four types of hybrid compounds relies on the Fmoc strategy and circumvents subsequent HPLC purification by precipitating the final product from organic solution in pure form. Hexa- and octapeptide pendants with internal di- and tetrapeptide bridges are now amenable in high yields to combinatorial synthesis of compound libraries for high-throughput screening purposes. Solid-phase peptide synthesis (SPPS) on an acid-resistant PAM allows us, after PMB deprotection, to subject the free aminopyrazole binding sites in an immobilized state to on-bead assays with fluorescence-labeled peptides. From the fluorescence emission intensity decrease, individual binding constants can be calculated via reference curves by simple application of the law of mass action. Gratifyingly, host/guest complexation can be monitored quantitatively even for those ligands, which are almost insoluble in water.lld:pubmed
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pubmed-article:17428094pubmed:monthMaylld:pubmed
pubmed-article:17428094pubmed:issn0022-3263lld:pubmed
pubmed-article:17428094pubmed:authorpubmed-author:SchraderThoma...lld:pubmed
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pubmed-article:17428094pubmed:pagination3614-24lld:pubmed
pubmed-article:17428094pubmed:dateRevised2010-11-18lld:pubmed
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pubmed-article:17428094pubmed:year2007lld:pubmed
pubmed-article:17428094pubmed:articleTitleSynthesis and binding studies of Alzheimer ligands on solid support.lld:pubmed
pubmed-article:17428094pubmed:affiliationFachbereich Chemie, Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.lld:pubmed
pubmed-article:17428094pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:17428094pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed