Tbuo-C20-gamma-glu(aeea)-otbu
[CAS 2645421-68-5]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: Tbuo-C20-gamma-glu(aeea)-otbu
• Synonyms: 2-[2-[2-[[(4S)-5-[(2-methylpropan-2-yl)oxy]-4-[[20-[(2-methylpropan-2-yl)oxy]-20-oxoicosanoyl]amino]-5-oxopentanoyl]amino]ethoxy]ethoxy]acetic acid
• Molecular Formula: C₃₉H₇₂N₂O₁₀
• Molecular Weight: 729.00
• CAS Registry Number: 2645421-68-5
• SMILES: CC(C)(C)OC(=O)CCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCOCCOCC(=O)O)C(=O)OC(C)(C)C

Properties

• Density: 1.0 g/cm³ Calc.^*
• Boiling point: 830.2 °C 760 mmHg (Calc.)^*
• Flash point: 455.9 °C (Calc.)^*
• Index of refraction: 1.4797624 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety 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

Discovery and Applications

tBuO-C20-γ-Glu(AEEA)-OtBu (CAS No. 2645421-68-5) is a synthetic peptide-linker building block used in the preparation of advanced peptide therapeutics and long-acting drug conjugates. It belongs to a class of multifunctional amino acid–based spacers that incorporate lipid chains, polyethylene glycol (PEG)-like units, and protected amino acid residues. This compound is not a natural product but a designed intermediate developed to enable controlled assembly of complex peptide drug structures used in modern pharmaceutical research, particularly for incretin-based metabolic therapies.

The emergence of this compound is tied to the rapid development of peptide drug engineering in the early twenty-first century, when pharmaceutical research increasingly focused on improving the pharmacokinetic properties of peptide therapeutics. Native peptides such as glucagon-like peptide-1 (GLP-1) and related analogs are rapidly degraded in vivo, which led to the development of chemical modification strategies aimed at prolonging half-life. These strategies include lipidation, PEGylation, and attachment of bulky linker systems that enhance albumin binding and reduce renal clearance. tBuO-C20-γ-Glu(AEEA)-OtBu is part of this broader technological framework.

The structure of this compound consists of three major functional regions. A long C20 aliphatic chain provides a hydrophobic lipid-like segment that promotes strong binding to serum albumin, a widely used strategy for extending circulation time of peptide drugs. The γ-glutamic acid unit serves as a branching and conjugation point, allowing controlled attachment to peptide backbones while providing enzymatically and chemically stable linkage geometry. The AEEA (aminoethoxyethoxyacetic acid) segment introduces a flexible, hydrophilic spacer similar in function to short polyethylene glycol chains, improving solubility and spatial separation between functional domains. Terminal tert-butyl ester protecting groups (tBuO / OtBu) are used during synthesis to prevent premature side reactions at carboxylic acid sites and are removed in later deprotection steps during final assembly.

The compound was developed within the context of peptide linker optimization for long-acting GLP-1 receptor agonists and dual- or triple-agonist metabolic drugs. In such systems, linker design is critical because it determines how the active peptide interacts with plasma proteins, how it is processed enzymatically, and how it is released or remains bound in circulation. The combination of lipid chain and polar spacer elements in tBuO-C20-γ-Glu(AEEA)-OtBu reflects a rational design approach aimed at balancing hydrophobic albumin affinity with aqueous solubility and synthetic tractability.

In pharmaceutical synthesis, this compound functions as a protected intermediate rather than an active drug substance. It is incorporated into larger peptide structures through stepwise coupling reactions, typically solid-phase peptide synthesis or solution-phase conjugation strategies. After coupling, the tert-butyl protecting groups are removed under acidic conditions to yield the final functional linker within the peptide framework. This modular approach allows precise control over pharmacokinetic properties without altering the biological activity of the peptide core.

The application of linker systems containing γ-glutamic acid and PEG-like spacers has been documented in multiple long-acting peptide drugs that target metabolic diseases such as type 2 diabetes and obesity. These systems aim to achieve sustained receptor activation while reducing dosing frequency. The inclusion of long-chain lipid moieties similar to the C20 segment is a well-established method for enhancing plasma protein binding and extending in vivo half-life.

From a chemical perspective, tBuO-C20-γ-Glu(AEEA)-OtBu is characterized by a high molecular weight and a combination of hydrophobic and hydrophilic domains. Its reactivity is governed primarily by the protected carboxyl groups and amide-forming functional sites that are revealed after deprotection steps. The compound is therefore used exclusively in controlled synthetic environments rather than as a final pharmacologically active substance.

Overall, tBuO-C20-γ-Glu(AEEA)-OtBu represents a modern class of rationally designed peptide linker intermediates used in the construction of long-acting therapeutic peptides. Its significance lies in its role as a modular structural element that enables the integration of lipid, peptide, and PEG-like components into a single framework, supporting the development of next-generation metabolic disease therapies with improved pharmacokinetic performance.