Related Experiment Video
Updated: Jun 30, 2026
07:11
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Acid promoted cinnamyl ion mobility within peptide derived macrocycles
Hongda Zhao1, Lidet Negash, Qi Wei
1Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, USA.
Journal of the American Chemical Society
|September 25, 2008
Summary
Researchers developed a novel method to create cyclic peptide structures with enhanced properties. This process yielded a molecule that promotes neurogenesis in adult mouse brains, offering potential therapeutic applications.
Area of Science:
- Chemical Synthesis
- Medicinal Chemistry
- Neuroscience
Background:
- Peptides are crucial biomolecules but often suffer from poor stability and membrane permeability.
- Restricting peptide conformational mobility can enhance stability and introduce new functionalities.
Purpose of the Study:
- To develop a method for creating conformationally restricted cyclic peptides with altered properties.
- To synthesize novel macrocyclic ethers and peptidomimetics.
- To identify bioactive molecules from these synthesized libraries.
Main Methods:
- Utilized a staged activation of a lipophilic reagent (reagent 2) for integration into peptides.
- Formed macrocyclic ethers through a two-step process involving reagent 2 and peptides.
- Induced structural modifications and cyclizations using protic acid treatment in anhydrous solvent.
Main Results:
- Successfully synthesized macrocyclic ethers (e.g., compound 4) and complex macrocycles (e.g., compound 15) from peptides.
- Demonstrated intramolecular cinnamyl unit migration and subsequent C-C bond formation.
- Identified a small molecule from the synthesized library that selectively promotes hippocampal neurogenesis.
Conclusions:
- The developed method allows systematic access to complex peptidomimetics with defined shapes and improved membrane properties.
- The identified neurogenic compound shows potential for therapeutic intervention in adult neurogenesis.
Related Concept Videos
00:57Cationic Chain-Growth Polymerization: Mechanism
The cationic polymerization mechanism consists of three steps: initiation, propagation, and termination. In the initiation step of the polymerization process, the π bond of a monomer gets protonated by the Lewis acid catalyst, which is formed from boron trifluoride and water. The protonation of the π bond generates a carbocation stabilized by the electron‐donating group. In the propagation step, the π bond of the second monomer acts as a nucleophile and attacks the generated carbocation,...
01:21Chemical Ionization (CI) Mass Spectrometry
The molecular ion peak of a molecule in the mass spectrum provides vital information for molecular identification. However, conventional electron impact ionization can lead to the rapid dissociation of some molecular ions before they reach the detector. A milder ionization method is required to increase the lifetime of such ionized analyte molecules. Chemical ionization (CI) is a gas-phase protonation reaction useful for mass-analyzing analyte molecules that are easily protonated to yield the...
01:20Anionic Chain-Growth Polymerization: Overview
The polymerization process that involves carbanion as an intermediate is called anionic polymerization. It is also a type of addition or chain-growth polymerization. Anionic polymerization gets initiated by a strong nucleophile such as an organolithium or a Grignard reagent. The most commonly used initiator for anionic polymerization is butyl lithium. Monomers involved in anionic polymerization must possess a vinyl group bonded to one or two electron-withdrawing groups. For instance,...
01:11ortho–para-Directing Activators: –CH3, –OH, –NH2, –OCH3
All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
01:16Cycloaddition Reactions: MO Requirements for Thermal Activation
Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.
01:04Anionic Chain-Growth Polymerization: Mechanism
The mechanism for anionic chain-growth polymerization involves initiation, propagation, and termination steps. In the initiation step, a nucleophilic anion, such as butyl lithium, initiates the polymerization process by attacking the π bond of the vinylic monomer. As a result, a carbanion, stabilized by the electron‐withdrawing group, is generated. The resulting carbanion acts as a Michael donor in the propagation step and attacks the second vinylic monomer, which acts as a Michael acceptor.