Tryptophan Analogues with Fixed Side-Chain Orientation: Expanding the Scope

Lennart Nicke; Philip Horx; Ronny Müller; Sylvia Els-Heindl; Armin Geyer

doi:10.1002/cbic.202000424

Tryptophan Analogues with Fixed Side-Chain Orientation: Expanding the Scope

Chembiochem. 2021 Jan 15;22(2):330-335. doi: 10.1002/cbic.202000424. Epub 2020 Sep 24.

Authors

Lennart Nicke¹, Philip Horx¹, Ronny Müller², Sylvia Els-Heindl², Armin Geyer¹

Affiliations

¹ Faculty of Chemistry, Philipps-University Marburg, Hans-Meerwein-Strasse 4, 35032, Marburg, Germany.
² Faculty of Life Sciences, Institute of Biochemistry, Leipzig University, Brüderstrasse 34, 04103, Leipzig, Germany.

Abstract

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.

Keywords: NMR spectroscopy; ghrelin; metadynamics; peptide; tryptophan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Indoles / chemistry
Molecular Structure
Peptides / chemistry
Tryptophan / analogs & derivatives
Tryptophan / chemical synthesis
Tryptophan / chemistry*

Substances

Indoles
Peptides
Tryptophan