Fmoc-His-Aib-OH
[CAS# 1446013-07-5]

Identification

• Classification: Biochemical >> Amino acids and their derivatives
• Name: Fmoc-His-Aib-OH
• Synonyms: 2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(1H-imidazol-5-yl)propanoyl]amino]-2-methylpropanoic acid
• Protein Sequence: HX
• Molecular Formula: C₂₅H₂₆N₄O₅
• Molecular Weight: 462.50
• CAS Registry Number: 1446013-07-5
• SMILES: CC(C)(C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)OCC2C3=CC=CC=C3C4=CC=CC=C24

Properties

• Density: 1.3±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.627, Calc.^*
• Boiling Point: 838.1±65.0 ºC (760 mmHg), Calc.^*
• Flash Point: 460.7±34.3 ºC, Calc.^*

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

Discovory and Applicatios

Fmoc-His-Aib-OH is a chemically significant compound used extensively in the field of peptide synthesis. It combines the structural and functional benefits of histidine and alpha-aminoisobutyric acid (Aib), with the N-terminal protected by the 9-fluorenylmethoxycarbonyl (Fmoc) group. This design allows the compound to play a critical role in the synthesis of bioactive peptides, providing stability and reactivity essential for diverse applications.

Histidine is a versatile amino acid characterized by its imidazole side chain, which is capable of participating in proton transfer, hydrogen bonding, and coordination with metal ions. These properties make it invaluable in enzymatic reactions and catalytic processes. Aib, a non-natural amino acid, is known for its ability to induce helicity in peptide structures. The inclusion of Aib promotes the formation of stable secondary structures such as 3_10-helices or α-helices, which are essential in the development of peptides with specific biological activities.

The discovery of Fmoc-His-Aib-OH can be attributed to advancements in solid-phase peptide synthesis (SPPS). The Fmoc group’s introduction provided a reliable method for the temporary protection of the amino group, enabling selective deprotection under mild conditions. This orthogonal strategy facilitated the efficient assembly of peptides containing sensitive functional groups, including those present in histidine. The combination of histidine and Aib was specifically designed to harness the structural rigidity of Aib and the functional versatility of histidine, leading to the synthesis of peptides with unique properties.

Fmoc-His-Aib-OH is synthesized using standard peptide coupling techniques. Initially, Fmoc-His is prepared by attaching the Fmoc group to the amino functionality of histidine under controlled conditions. This intermediate is then coupled with Aib using reagents like HBTU (O-Benzotriazole-N,N,N’,N’-tetramethyluronium hexafluorophosphate) or HATU in the presence of a base such as N,N-Diisopropylethylamine (DIPEA). The reaction ensures efficient peptide bond formation while minimizing side reactions. The product is purified using high-performance liquid chromatography (HPLC) to achieve the required level of purity for downstream applications.

One of the most notable applications of Fmoc-His-Aib-OH is in the design of helical peptides. These peptides are employed in various biomedical and pharmaceutical research areas, including the development of antimicrobial agents and enzyme mimetics. The ability of Aib to enforce a helical conformation enhances the structural stability and biological activity of the synthesized peptides. Additionally, histidine’s functional side chain allows these peptides to interact with biological targets in a highly specific manner. This makes Fmoc-His-Aib-OH a valuable building block in creating peptides for therapeutic and diagnostic purposes.

Another critical area of application is the study of protein-protein interactions. By incorporating Fmoc-His-Aib-OH into synthetic peptides, researchers can mimic key structural motifs found in natural proteins, providing insights into molecular recognition and binding mechanisms. The compound’s versatility extends to its use in creating pH-sensitive peptides, which are increasingly explored for targeted drug delivery systems.