Sigma-Aldrich™ HATU 97%, for peptide synthesis

HATU (O-(7-Azabenzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate) is a highly efficient amide bond-forming reagent commonly used in solid-phase peptide synthesis (SPPS), pharmaceutical research, and organic chemistry. This reagent:

• Activates carboxyl groups efficiently, leading to rapid and high-yielding peptide bond formation.
• Minimizes racemization, making it an excellent alternative to HBTU and other uronium-based coupling reagents.
• Provides high coupling efficiency in the synthesis of difficult peptide sequences, including sterically hindered and β-sheet-prone peptides.
• Enhances regioselectivity in amide bond formation, allowing for cleaner reactions and higher product purity.

HATU is widely used in peptide synthesis, amide coupling reactions, and bioconjugation strategies, making it a preferred reagent in academic and industrial peptide production.

Key Features & Benefits

✔ High Coupling Efficiency – Forms high-yielding amide bonds even in challenging sequences.

✔ Minimizes Racemization – Reduces epimerization compared to HBTU, DIC, and PyBOP.

✔ Compatible with SPPS & Solution-Phase Synthesis – Suitable for both automated and manual peptide synthesis methods.

✔ Fast Reaction Kinetics – Enhances amide bond formation rates while maintaining high selectivity.

✔ Stable & Versatile – Can be used in carbodiimide-free coupling methods, preventing side reactions.

✔ Well-Characterized & Reliable – Verified via HPLC, melting point analysis, and purity assays.

Chemical Properties & Identifiers

Applications

🔹 Peptide Synthesis & Proteomics Research – Used in Fmoc-based SPPS for high-efficiency amide bond formation.

🔹 Pharmaceutical & Drug Discovery – Essential for peptide drug synthesis and modification.

🔹 Organic Synthesis & Bioconjugation – Enhances amide bond selectivity and functionalization.

🔹 Selective Acylation & Cyclization Reactions – Used in macrocycle formation and bioactive molecule design.

✔ Reported Applications Include:

1️⃣ Aurora A Kinase Inhibitor Synthesis – Applied in targeted drug development for cancer research.

2️⃣ HPLC Enantiomeric Analysis – Used to determine D- and L- acid enantiomers in human plasma.

3️⃣ Peptide Coupling & Solid-Phase Synthesis – Facilitates high-yield amide bond formation in difficult sequences.

4️⃣ N-Arylsulfonamide Peptide Synthesis – Applied in solid-phase approaches to novel peptide-drug conjugates.

Reaction Mechanism & Workflow

HATU-Catalyzed Peptide Coupling Mechanism

1️⃣ Carboxyl Activation – HATU reacts with carboxylic acids (-COOH) in the presence of a base (DIPEA or NMM).

2️⃣ Activated Onium Intermediate Formation – Forms an electron-rich activated ester that enhances amide bond formation.

3️⃣ Nucleophilic Attack – The amine (-NH₂) nucleophile attacks the activated carboxyl group, forming the desired amide bond.

4️⃣ Byproduct Removal – HATU decomposes into a non-reactive hydroxytriazole derivative, minimizing racemization.

✔ Recommended Reaction Conditions:

• Solvent: DMF, DCM, or NMP
• Base: DIPEA (Diisopropylethylamine) or NMM (N-Methylmorpholine)
• Reaction Temperature: Room temperature (20-25°C)

Storage & Handling

📦 Storage Conditions:

• Store at 2-8°C in a dry, tightly sealed container.
• Protect from moisture and prolonged air exposure.
• Dissolve in anhydrous DMF or DCM before use.

⚠ Handling Precautions:

• Use in a fume hood to prevent inhalation of dust.
• Wear gloves, lab coat, and safety goggles while handling.
• Dispose of waste properly according to laboratory regulations.

General References & Research Citations

1️⃣ HATU in Peptide Synthesis & Coupling Strategies – Org. Biomol. Chem., 2021, 19(6), 1573-1581.

2️⃣ Comparison of Peptide Coupling Reagents (HATU vs. HBTU) – J. Pept. Sci., 2019, 25(3), 224-232.

3️⃣ HATU in Drug Development for Kinase Inhibition – J. Med. Chem., 2020, 63(14), 7490-7503.

Regulatory & Safety Information

⚠ For Research Use Only (RUO) – Not intended for diagnostic or therapeutic applications.

⚠ Hazard Warnings: Follow standard lab safety protocols when handling.

Ordering Information

📦 Shipping Conditions: Ambient

Sigma-Aldrich™ HATU (≥97%) is a highly efficient peptide coupling reagent, ideal for amide bond formation, solid-phase peptide synthesis (SPPS), and organic synthesis. With low racemization, high stability, and rapid reaction kinetics, it is a preferred choice in pharmaceutical research, peptide therapeutics, and bioconjugation strategies.