Fmoc-His-Aib-OH TFA
[CAS# 1446013-08-6]

Identification

• Classification: Biological >> Proteins and peptides
• Name: Fmoc-His-Aib-OH TFA
• Synonyms: 2-[(2S)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(1H-imidazol-5-yl)propanamido]-2-methylpropanoic acid; trifluoroacetic acid
• Molecular Formula: C₂₅H₂₆N₄O₅^.C₂HF₃O₂
• Molecular Weight: 576.52
• CAS Registry Number: 1446013-08-6
• EC Number: 815-122-7
• SMILES: CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)N)O

Safety Data

• Hazard Symbols: GHS05 Danger
• Hazard Statements: H318
• Precautionary Statements: P264+P265-P280-P305+P354+P338-P317

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Serious eye damage	Eye Dam.	1	H318

Discovory and Applicatios

Fmoc-His-Aib-OH·TFA is a synthetic peptide derivative that has its origin in the development of solid-phase peptide synthesis techniques, particularly those relying on 9-fluorenylmethoxycarbonyl (Fmoc) chemistry. The discovery of Fmoc as a protecting group in the late 1970s and early 1980s provided chemists with a reliable strategy to assemble peptides under mild conditions, allowing for base-labile removal of the Fmoc group without affecting acid-sensitive side-chain protecting groups. The introduction of this method revolutionized peptide synthesis by providing improved yields, reduced side reactions, and greater flexibility in protecting group strategies. Fmoc-His-Aib-OH·TFA is an example of a derivative designed for sequential incorporation into peptide chains, taking advantage of these developments.

Histidine, one of the essential amino acids, plays an important role in protein chemistry because of the imidazole side chain, which can function as both a proton donor and acceptor under physiological pH conditions. Its incorporation into synthetic peptides often introduces functional properties such as metal ion coordination, catalytic activity, or stabilization of protein folding. To prevent undesired reactivity during synthesis, histidine is typically protected at the N-terminus by the Fmoc group, ensuring selective deprotection and coupling in a stepwise fashion. In Fmoc-His-Aib-OH·TFA, the Fmoc group safeguards the amino function, enabling the controlled extension of the peptide sequence.

Aib, or α-aminoisobutyric acid, is a non-proteinogenic amino acid first identified in natural peptides such as alamethicin, produced by certain strains of the fungus Trichoderma. Its presence in peptides is of particular interest because it has been shown to strongly induce helical conformations. This effect results from the steric hindrance of its gem-dimethyl substitution at the α-carbon, which limits backbone flexibility and drives the peptide chain into well-defined secondary structures. The incorporation of Aib into synthetic peptides has been widely studied as a means of designing molecules with enhanced conformational stability, which is valuable for structural investigations and the development of therapeutic peptides resistant to enzymatic degradation.

The compound Fmoc-His-Aib-OH·TFA combines these features into a dipeptide building block. The free carboxyl group allows coupling at the C-terminus, while the Fmoc group permits controlled deprotection and extension at the N-terminus. The presence of histidine introduces the possibility of functional interactions, while Aib contributes conformational constraints. The TFA component indicates that the compound is isolated as a trifluoroacetate salt, a common practice in peptide chemistry where TFA is used for deprotection and purification. This salt form improves handling and solubility, while maintaining stability for storage and subsequent use.

Applications of Fmoc-His-Aib-OH·TFA are found in synthetic peptide research, particularly in the design of helical peptides, peptidomimetics, and foldamers. The dipeptide has been employed in efforts to study helix stabilization, test hypotheses about peptide folding pathways, and create scaffolds for drug discovery. In medicinal chemistry, histidine-containing Aib peptides have been explored for their ability to mimic enzyme active sites or interact selectively with biomolecular targets. Furthermore, the inclusion of Aib often results in peptides that are less susceptible to proteolytic breakdown, enhancing their potential as therapeutic agents. The ability to systematically incorporate such residues using protected derivatives like Fmoc-His-Aib-OH·TFA has made it possible to engineer peptides with defined structural and functional characteristics, advancing both fundamental research and applied biomedical science.

Through the availability of protected dipeptides such as Fmoc-His-Aib-OH·TFA, peptide chemistry continues to benefit from the combined insights of synthetic methodology, natural product discovery, and structural biology. This compound stands as a practical example of how carefully designed building blocks can serve as the foundation for new discoveries in peptide-based science and technology.