-Sheet Ligands in Action: KLVFF Recognition by Aminopyrazole Hybrid Receptors in Water
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- 作者：Petra Rzepecki and Thomas Schrader
- 刊名：Journal of the American Chemical Society
- 出版年：2005
- 出版时间：March 9, 2005
- 年：2005
- 卷：127
- 期：9
- 页码：3016 - 3025
- 全文大小：267K
- 年卷期：v.127,no.9(March 9, 2005)
- ISSN：1520-5126
文摘
Little is known about the precise mechanism of action of 
-sheet ligands, hampered by thenotorious solubility problems involved with protein misfolding and amyloid formation. Recently the nucleationsite for the pathogenic aggregation of the Alzheimer's peptide was identified as the KLVFF sequence inthe central region of A. A combination of two aminopyrazole ligands with di- or tripeptides taken from thiskey fragment now furnished water-soluble A-specific ligands which allow model investigations in water. Adetailed conformational analysis provides experimental evidence for an increased -sheet content inducedin the peptide. Strong indications were also found for the peptide backbone recognition via hydrogen bondsplus hydrophobic contributions between aminopyrazole nuclei and Phe residues. The affinity of these newligands toward the KKLVFF fragment is highly dependent on their sequence and composition from naturaland artificial amino acids. Thus, for the first time, detailed insight is gained into the complexation of -sheetligands with model peptides taken directly from A.
-sheet ligands, hampered by thenotorious solubility problems involved with protein misfolding and amyloid formation. Recently the nucleationsite for the pathogenic aggregation of the Alzheimer's peptide was identified as the KLVFF sequence inthe central region of A. A combination of two aminopyrazole ligands with di- or tripeptides taken from thiskey fragment now furnished water-soluble A-specific ligands which allow model investigations in water. Adetailed conformational analysis provides experimental evidence for an increased -sheet content inducedin the peptide. Strong indications were also found for the peptide backbone recognition via hydrogen bondsplus hydrophobic contributions between aminopyrazole nuclei and Phe residues. The affinity of these newligands toward the KKLVFF fragment is highly dependent on their sequence and composition from naturaland artificial amino acids. Thus, for the first time, detailed insight is gained into the complexation of -sheetligands with model peptides taken directly from A.