Related Experiment Video
Updated: May 5, 2026
13:37
Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library
Published on: June 20, 2014
18.1K
Triazination/IEDDA Cascade Modular Strategy Installing Pyridines/Pyrimidines onto Tyrosine Enables Peptide Screening
Quan Zuo1, Xinyi Song2, Jie Yan1
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P. R. China.
Journal of the American Chemical Society
|January 31, 2025
Summary
We developed a novel Tyrosine-1,2,3-Triazine Ligation (YTL) strategy for peptide modification. This method enables rapid derivatization of tyrosine-containing peptides, leading to potential antibacterial candidates like Z8.
Area of Science:
- Chemical Biology
- Medicinal Chemistry
- Peptide Therapeutics
Background:
- Modular chemical postmodification of peptides is crucial for optimizing peptide therapeutics.
- Current methods often require non-natural amino acids and limit peptide diversity.
Purpose of the Study:
- To develop a new, versatile strategy for modular peptide postmodification.
- To overcome limitations of existing bio-orthogonal and ligation techniques.
Main Methods:
- Development of the Tyrosine-1,2,3-Triazine Ligation (YTL) strategy.
- A "one-pot, two-step" process combining SNAr and IEDDA reactions.
- Application to solid-phase postmodification of various biorelated peptides.
Main Results:
- Successful synthesis of dual-mode imaging probes and long-acting GLP-1 analogs.
- Construction of a 384-amphipathic peptide library using YTL.
- Identification of Z8 as a potential antibacterial candidate from 20 RYR derivatives.
Conclusions:
- The YTL strategy enables efficient modular postmodification of tyrosine-containing peptides.
- YTL expands possibilities for peptide therapeutic innovation and drug discovery.
- The identified Z8 derivative shows promise as a novel antibacterial agent.
Related Concept Videos
01:20Amides to Amines: LiAlH4 Reduction
5.6K
Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
5.6K
01:13meta-Directing Deactivators: –NO2, –CN, –CHO, –CO2R, –COR, –CO2H
4.6K
All meta-directing substituents are deactivating groups. These substituents withdraw electrons from the aromatic ring, making the ring less reactive toward electrophilic substitution. For example, the nitration of nitrobenzene is 100,000 times slower than that of benzene because of the deactivating effect of the nitro group. The first step in an electrophilic aromatic substitution is the addition of an electrophile to form a resonance-stabilized carbocation. The energy diagrams for...
4.6K
01:19Diazonium Group Substitution: –OH and –H
1.9K
Nitrous acid, a weak acid, is prepared in situ via the reaction of sodium nitrite with a strong acid under cold conditions. This nitrous acid prepared in situ reacts with primary arylamines to form arenediazonium salts. Such reactions are known as diazotization reactions. As shown in Figure 1, the formation of arenediazonium salts begins with the decomposition of nitrous acid in an acidic solution to give nitrosonium ions.
1.9K
01:26EDTA: Auxiliary Complexing Reagents
1.6K
EDTA titrations are usually carried out in highly basic conditions, where the fully deprotonated form of EDTA, Y4−, actively complexes with the free metal ions in the solution. Several metal ions precipitate as hydrous oxide (hydroxides, oxides, or oxyhydroxides) under these conditions, lowering the concentration of free metal ions in the solution. For this reason, auxiliary complexing agents or ligands such as ammonia, tartrate, citrate, or triethanolamine are used in EDTA titrations to...
1.6K
01:28Bioreactor Controls-I
103
Maintaining optimal conditions within fermenters is essential for maximizing microbial productivity and ensuring process efficiency. This lesson focuses on key parameters—temperature, foam, pH, carbon dioxide, oxygen, and pressure—and their precise measurement and control strategies in fermentation systems.Temperature ControlTemperature regulation is critical due to the exothermic nature of many fermentation processes. In small laboratory fermenters, temperature is commonly...
103
01:28Methods of Medium Optimization
74
Optimizing growth media enhances microbial proliferation and maximizes product yield. Statistical experimental design methodologies provide structured and reproducible approaches, offering progressively higher levels of robustness and efficiency.The One-Factor-at-a-Time (OFAT) MethodThe One-Factor-at-a-Time (OFAT) method involves adjusting a single variable while keeping all others constant. However, it cannot detect interactions between variables, often leading to suboptimal outcomes when...
74