Tryptophan Analogues with Fixed Side‐Chain Orientation: Expanding the Scope
| Autor: | Philip Horx, Armin Geyer, Sylvia Els-Heindl, Ronny Müller, Lennart Nicke |
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| Rok vydání: | 2020 |
| Předmět: |
Indoles
Stereochemistry Peptide 010402 general chemistry 01 natural sciences Biochemistry metadynamics Bioactive peptide NMR spectroscopy Side chain Inverse agonist Molecular Biology Indole test chemistry.chemical_classification Molecular Structure 010405 organic chemistry Communication Organic Chemistry Tryptophan Nuclear magnetic resonance spectroscopy Communications peptide 0104 chemical sciences Amino acid chemistry ghrelin Molecular Medicine Peptides |
| Zdroj: | Chembiochem |
| ISSN: | 1439-7633 1439-4227 |
| DOI: | 10.1002/cbic.202000424 |
| Popis: | A generalized synthetic strategy is proposed here for the synthesis of asymmetric β‐indoylated amino acids by 8‐aminoquinoline (8AQ)‐directed C(sp3)‐H functionalization of suitably protected precursors. Peptides containing one of the four stereoisomers of (indol‐3‐yl)‐3‐phenylalanine at position 2 of the parent peptide KwFwLL‐NH2 (w=d‐Trp) cover a wide range of activities as ghrelin receptor inverse agonists, among them the most active described until now. This application exemplarily shows how β‐indoylated amino acids can be used for the systematic variation of the position of an indole group in a bioactive peptide. Immobile indole stays put: Conformationally locked side‐chain rotamers of tryptophan were obtained by a general β‐indoylation method. The new type of β‐indoyl‐α‐amino acids allow systematic optimization of the β‐indole group orientation in different peptide environments. Four ghrelin receptor inverse agonists containing stereoisomeric β‐indoylated α‐amino acids span a broad range of activities. |
| Databáze: | OpenAIRE |
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