Fmoc-Ile-Aib-OH
[CAS# 2171139-20-9]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives
• Name: Fmoc-Ile-Aib-OH
• Synonyms: 2-[[(2S,3S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methylpentanoyl]amino]-2-methylpropanoic acid
• Protein Sequence: IX
• Molecular Formula: C₂₅H₃₀N₂O₅
• Molecular Weight: 438.52
• CAS Registry Number: 2171139-20-9
• SMILES: CC[C@H](C)[C@@H](C(=O)NC(C)(C)C(=O)O)NC(=O)OCC1C2=CC=CC=C2C3=CC=CC=C13

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 682.5±45.0 ºC 760 mmHg (Calc.)^*
• Flash point: 366.5±28.7 ºC (Calc.)^*
• Index of refraction: 1.572 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Discovory and Applicatios

Fmoc-Ile-Aib-OH is a protected dipeptide derivative that is widely used in peptide synthesis. It contains the Fmoc (9-fluorenylmethoxycarbonyl) protecting group at the N-terminus, which is a standard removable protecting group in solid-phase peptide synthesis. The dipeptide backbone consists of isoleucine (Ile), a branched-chain hydrophobic amino acid, and α-aminoisobutyric acid (Aib), a non-proteinogenic amino acid characterized by two methyl groups attached to the α-carbon. The C-terminus of the dipeptide is present as a free carboxylic acid (-OH), which allows further coupling in peptide chain elongation.

The discovery and application of Fmoc-Ile-Aib-OH are closely connected to the development of synthetic peptide chemistry, especially the use of Aib-containing sequences to study secondary structures. Aib is known to strongly favor helical conformations due to its steric constraints, and incorporation of Aib into peptides induces stable helical structures even in short sequences. The use of Fmoc-protected dipeptides such as Fmoc-Ile-Aib-OH enables researchers to introduce structural motifs that control peptide conformation and stability.

In peptide synthesis, Fmoc-Ile-Aib-OH serves as a building block for preparing synthetic peptides with enhanced conformational rigidity. The Fmoc group can be removed under mild basic conditions, typically with piperidine in dimethylformamide, leaving the amino group available for coupling with additional amino acids. The carboxylic acid terminus can be activated using standard coupling agents, allowing straightforward integration into growing peptide chains. The presence of Aib within the sequence helps to stabilize α-helical or 3₁₀-helical conformations, making such peptides valuable tools for structural studies.

Applications of Fmoc-Ile-Aib-OH extend across medicinal chemistry, structural biology, and materials science. In medicinal chemistry, Aib-containing peptides have been studied for their ability to resist enzymatic degradation, improving pharmacokinetic properties compared to natural peptides. These stabilized peptides are of interest in the design of peptide-based therapeutics, such as receptor agonists, enzyme inhibitors, and antimicrobial agents. The Ile-Aib sequence specifically contributes to amphipathic helices that are important in membrane interactions.

In structural biology, Fmoc-Ile-Aib-OH is used in the synthesis of model peptides that mimic protein secondary structures. Because Aib enforces helicity, these peptides provide insights into folding, stability, and interactions of helical motifs in proteins. They are also used in spectroscopic studies, such as circular dichroism and NMR, to understand conformational preferences and dynamics.

In materials science, Aib-containing peptides synthesized from Fmoc-Ile-Aib-OH are employed in designing peptide-based nanostructures, gels, and biomaterials. The conformational rigidity and predictable folding patterns imparted by Aib are exploited in creating ordered molecular assemblies. These applications demonstrate how synthetic dipeptides can extend beyond biochemical studies to the development of functional materials.

The introduction of dipeptide building blocks like Fmoc-Ile-Aib-OH into synthetic peptide chemistry represents an important step in advancing the ability to control peptide structure and function. By combining natural amino acids such as isoleucine with non-proteinogenic residues like Aib, researchers can design peptides with tailored conformational properties, improved stability, and specific biological functions. This dual advantage of synthetic flexibility and structural precision ensures that Fmoc-Ile-Aib-OH continues to play a role in diverse areas of research and application.

References

2024. Preparation method of N-(N-(9-fluorenylmethoxycarbonyl)-L-isoleucylaminocarboxyl)-2-aminoisobutyric acid. Publication Number: CN-119350432-A.
2023. Short peptide Fmoc-L-Ile-Aib-OH and its preparation method. Publication Number: CN-116425827-A.
2023. A kind of synthetic method of Tirzepatide. Publication Number: CN-115651075-B.