# Pseudo‐Ring Methodology to Control the Conformations of Macrocyclic Peptides

## TL;DR

This paper introduces a method using pseudo-rings to control the shape and properties of macrocyclic peptides, enabling tunable characteristics like lipophilicity and fluorescence.

## Contribution

The novelty lies in using pseudo-rings to dynamically control macrocyclic peptide conformations from a single building block.

## Key findings

- Pseudo-ring-containing macrocycles exhibit distinct 3D structures in open and closed forms.
- The conformational changes lead to differences in lipophilicity and tunable fluorescence.
- Pseudo-ring grafts offer a versatile tool for designing macrocyclic peptides with unique properties.

## Abstract

A pseudo‐ring is a medium‐sized cyclic structure, held together by a strong hydrogen bond, that can act as a mimetic of a covalently linked heterocycle. Molecules that contain pseudo‐rings can switch between “open” and “closed” forms. This paper examines the utility of pseudo‐ring constructs to control conformations and properties of macrocycles. The spectroscopic evidence suggests that the “open” and “closed” pseudo‐ring‐containing macrocycles differ in their three‐dimensional characteristics, which results in markedly different lipophilicities. The dynamic nature of pseudo‐rings has led to the emergence of tunable fluorescence that should be useful in environment‐sensitive applications.

Pseudo‐ring grafts represent a powerful conformational control tool in macrocyclic peptides. “Open” and “closed” conformations can be accessed from a single building block which allow for macrocyclic peptides with unique conformations, lipophilicities and fluorescence.
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