Oligo(N‐methylalanine) as a Peptide‐Based Molecular Scaffold with a Minimal Structure and High Density of Functionalizable Sites. Issue 14 (10th February 2022)

• Record Type: Journal Article
• Authors: Yokomine, Marin; Morimoto, Jumpei; Fukuda, Yasuhiro; Shiratori, Yota; Kuroda, Daisuke; Ueda, Takumi; Takeuchi, Koh; Tsumoto, Kouhei; Sando, Shinsuke
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 14(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-10
• Subjects: Conformational Analysis -- Functionalization -- Molecular Scaffolds -- Peptides -- Protein Ligands; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202200119
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Functionalizable synthetic molecules with nanometer sizes and defined shapes in water are useful as molecular scaffolds to mimic the functions of biomacromolecules and develop chemical tools for manipulating biomacromolecules. Herein, we propose oligo( N ‐methylalanine) (oligo‐NMA) as a peptide‐based molecular scaffold with a minimal structure and a high density of functionalizable sites. Oligo‐NMA forms a defined shape in water without hydrogen‐bonding networks or ring constraints, which enables the molecule to act as a scaffold with minimal atomic composition. Furthermore, functional groups can be readily introduced on the nitrogens and α‐carbons of oligo‐NMA. Computational and NMR spectroscopic analysis suggested that the backbone structure of oligo‐NMA is not largely affected by functionalization. Moreover, the usefulness of oligo‐NMA was demonstrated by the design of protein ligands. The ease of synthesis, minimal structure, and high functionalization flexibility makes oligo‐NMA a useful scaffold for chemical and biological applications. Abstract : Oligo( N ‐methylalanine) (oligo‐NMA) is proposed as a peptide‐based molecular scaffold with a minimal structure and a high density of functionalizable sites. Computational and NMR spectroscopic analysis suggested that the backbone structure of oligo‐NMA is not largely affected by functionalization. Moreover, the usefulness of oligo‐NMA as a molecular scaffold was demonstrated by the design of protein ligands.