Fmoc-Glu(OtBu)-Gly-OH
[CAS# 866044-63-5]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives
• Name: Fmoc-Glu(OtBu)-Gly-OH
• Synonyms: 2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]acetic acid
• Protein Sequence: XG
• Molecular Formula: C₂₆H₃₀N₂O₇
• Molecular Weight: 482.53
• CAS Registry Number: 866044-63-5
• SMILES: CC(C)(C)OC(=O)CC[C@@H](C(=O)NCC(=O)O)NC(=O)OCC1C2=CC=CC=C2C3=CC=CC=C13

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 748.2±60.0 ºC 760 mmHg (Calc.)^*
• Flash point: 406.3±32.9 ºC (Calc.)^*
• Index of refraction: 1.572 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319
• Precautionary Statements: P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Discovory and Applicatios

Fmoc-Glu(OtBu)-Gly-OH is a protected dipeptide derivative that plays an important role as a building block in modern peptide synthesis. The molecule contains several characteristic features that make it highly suitable for controlled synthetic applications. The N-terminus is protected with the Fmoc (9-fluorenylmethoxycarbonyl) group, a widely used base-labile protecting group in solid-phase peptide synthesis, which can be removed under mild basic conditions such as piperidine in dimethylformamide. The first amino acid residue is glutamic acid (Glu), a dicarboxylic amino acid that contains an additional carboxyl group in its side chain. In this compound, the side chain carboxyl is protected as a tert-butyl ester (OtBu), preventing side reactions during peptide coupling steps. The second amino acid is glycine (Gly), the simplest natural amino acid, which introduces flexibility due to the absence of a side chain beyond a hydrogen atom. The C-terminus of the dipeptide is present as a free carboxylic acid (-OH), enabling further elongation of the peptide chain.

The discovery of compounds such as Fmoc-Glu(OtBu)-Gly-OH arose from advances in peptide chemistry in the late 20th century, when orthogonal protecting group strategies were developed to allow the efficient synthesis of complex peptides. The introduction of the Fmoc group offered an alternative to earlier Boc-based methods, allowing selective deprotection under non-acidic conditions, which preserved acid-sensitive groups such as tert-butyl esters. The use of side-chain protection like OtBu was critical for glutamic acid, since unprotected side-chain carboxyls could interfere with peptide bond formation and reduce yields. By combining these elements, Fmoc-Glu(OtBu)-Gly-OH was designed to allow controlled incorporation of glutamic acid and glycine residues into longer peptide sequences without unwanted side reactions.

Applications of Fmoc-Glu(OtBu)-Gly-OH are mainly found in peptide synthesis, structural biology, and biomedical research. In peptide synthesis, this dipeptide is used as a pre-assembled fragment to simplify the construction of longer sequences. The Fmoc protection strategy enables automated solid-phase peptide synthesis, while the OtBu group ensures that the glutamic acid side chain remains protected until selective deprotection is desired, typically under acidic conditions. The presence of glycine adds flexibility to the peptide backbone and reduces steric hindrance, making this building block useful in sequences that require conformational adaptability.

In structural biology, peptides derived from Fmoc-Glu(OtBu)-Gly-OH are valuable for studying the role of acidic residues in protein folding and function. Glutamic acid residues are critical in forming salt bridges and hydrogen-bonding networks in proteins, and their controlled introduction into synthetic peptides allows researchers to investigate these interactions in detail. Glycine residues, in contrast, are often found in turns or flexible regions of proteins, and their inclusion in model peptides helps in understanding conformational dynamics.

In medicinal chemistry, peptides constructed from Fmoc-Glu(OtBu)-Gly-OH are of interest in the design of therapeutic peptides and peptidomimetics. Glutamic acid contributes to solubility and ionic interactions with biological targets, while glycine contributes to backbone flexibility. Together, they allow the design of sequences with balanced structural and functional properties. These synthetic peptides may be evaluated for enzyme inhibition, receptor binding, or antimicrobial activity, among other uses.

The development of Fmoc-Glu(OtBu)-Gly-OH illustrates the sophistication of modern peptide chemistry, where the careful choice of protecting groups and amino acid combinations enables precise control over peptide structure and reactivity. By integrating stability, flexibility, and orthogonal protection, it has become a valuable intermediate in both fundamental research and applied sciences.

References

2024. A preparation method of semaglutide. Publication Number: CN-117986349-B.
2023. Semex lattice Synthesis method of lupeptide. Publication Number: CN-116120427-B.
2022. GLP-1/GIP double agonist and preparation method and application thereof. Publication Number: CN-117402219-B.