Sieber Linker
[CAS# 3722-51-8]

Identification

• Classification: Flavors and spices >> Synthetic spice >> Lactone and oxygen-containing heterocyclic compound
• Name: Sieber Linker
• Synonyms: 3-Hydroxy-9H-xanthen-9-one
• Molecular Formula: C₁₃H₈O₃
• Molecular Weight: 212.20
• CAS Registry Number: 3722-51-8
• SMILES: C1=CC=C2C(=C1)C(=O)C3=C(O2)C=C(C=C3)O

Properties

• Density: 1.4±0.1 g/cm³, Calc.^*
• Melting point: 243 ºC
• Index of Refraction: 1.679, Calc.^*
• Boiling Point: 403.9±24.0 ºC (760 mmHg), Calc.^*
• Flash Point: 162.9±16.4 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319
• Precautionary Statements: P305+P351+P338

Discovory and Applicatios

The Sieber linker is a chemical moiety that plays a significant role in peptide synthesis and drug development, particularly in the context of solid-phase peptide synthesis (SPPS). Its introduction has greatly influenced the fields of medicinal chemistry and bioconjugation, offering enhanced strategies for peptide assembly and modification.

Developed in the early 1990s by Dr. Robert A. H. L. Sieber and his team, the Sieber linker was designed to improve the efficiency of peptide synthesis, addressing the limitations of traditional SPPS methods. Traditional approaches often faced challenges regarding the stability and release of synthesized peptides from solid supports. The Sieber linker was created to overcome these hurdles by providing a robust yet easily cleavable linkage between the peptide and the solid support. The linker comprises a phenolic group, which allows for mild cleavage conditions, thus enabling the selective release of the desired peptide while preserving its structural integrity.

One of the primary applications of the Sieber linker lies in the synthesis of peptide libraries for drug discovery. The capacity to generate large collections of peptides quickly and efficiently is crucial for identifying potential therapeutic candidates. By employing the Sieber linker, researchers can construct diverse peptide libraries that are amenable to high-throughput screening, facilitating the rapid evaluation of biological activity and efficacy. This capability is particularly beneficial in the early stages of drug development, where screening numerous compounds against specific biological targets is essential for discovering lead candidates.

Moreover, the Sieber linker has proven instrumental in developing peptide-based therapeutics. Peptides are increasingly recognized for their therapeutic potential due to their specificity and reduced side effects compared to traditional small-molecule drugs. The Sieber linker supports the synthesis of cyclic peptides, which often exhibit enhanced stability and bioactivity. These cyclic peptides serve as valuable leads for developing novel therapeutics targeting various diseases, including cancer, infectious diseases, and metabolic disorders.

The versatility of the Sieber linker extends beyond peptide synthesis to applications in bioconjugation, where it can facilitate the attachment of peptides to other biomolecules, such as proteins or nucleic acids. This ability to create multifunctional conjugates is critical for the design of targeted drug delivery systems and diagnostic agents, further broadening the scope of its applications in biomedical research.

In summary, the Sieber linker has become an indispensable tool in peptide synthesis and drug development, significantly advancing the methodologies employed in these fields. Its introduction has enabled researchers to create diverse peptide libraries for drug discovery, synthesize potent peptide-based therapeutics, and develop bioconjugates for targeted delivery systems. As the demand for innovative therapeutic agents continues to grow, the Sieber linker will likely play a pivotal role in shaping the future of peptide chemistry and medicinal applications.

References

2024. Exploring synthetic xanthone derivatives as potential anti-inflammatory agents: a comprehensive review. Chemical Papers, 78(8).
DOI: 10.1007/s11696-024-03614-z

2022. Synthesis and Antimicrobial and Antioxidant Activities of 1,2,3-Triazole-Tethered Xanthone Derivatives. Russian Journal of Organic Chemistry, 58(6).
DOI: 10.1134/s1070428022060173

1995. Use of XAL handles for solid-phase synthesis of peptide amides. Peptides 1994 [No volume/issue available].
DOI: 10.1007/978-94-011-1468-4_113