Synthesis and binding studies of Alzheimer ligands on solid support
| Autor: | Manuel Peifer, Nina Geib, Thomas Schrader, Petra Rzepecki, Frank Dr. Biesemeier |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
chemistry.chemical_classification
Amyloid beta-Peptides Tetrapeptide Molecular Structure Ligand Stereochemistry Organic Chemistry Chemie Peptide HEXA Ligands Chemical synthesis Inclusion compound Solutions chemistry.chemical_compound chemistry Alzheimer Disease Peptide synthesis Pyrazoles Binding site Peptides Amination |
| Zdroj: | The Journal of organic chemistry. 72(10) |
| ISSN: | 0022-3263 |
| Popis: | Aminopyrazole 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. |
| Databáze: | OpenAIRE |
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