Trimethylacetic anhydride

• CAS: 1538-75-6
• Catalog Number: ACM1538756
• Category: Acylation Reagents
• Molecular Weight: 186.25
• Molecular Formula: C10H18O3
• Synonyms: 2,2-Dimethylpropionic anhydride, Pivalic anhydride
• Boiling Point: 193 °C (lit.)
• Density: 0.918 g/mL at 25 °C (lit.)
• Physical State: Liquid

Case Study

Trimethylacetic Anhydride for Efficient Derivatization in MS-Based Histone PTM Quantification

Kuchaříková H, et al. Molecular & Cellular Proteomics, 2021, 20, 100114.

Trimethylacetic anhydride (TMA) has emerged as a powerful derivatization reagent in bottom-up proteomic workflows aimed at quantifying histone post-translational modifications (hPTMs). The protocol utilizes TMA to acylate primary amines present on lysine side chains and peptide N-termini generated by trypsin digestion. This modification is crucial for suppressing charge-induced peptide heterogeneity and enabling accurate MS1-level quantification. In the optimized method, histone proteins (H3 and H4) are first digested enzymatically, followed by TMA-based derivatization performed under microwave irradiation. This irradiation accelerates the reaction kinetics, shortening incubation to a few minutes while maintaining high derivatization yields-achieving >98% and >99% efficiencies for histone H4 and H3, respectively.
The derivatized peptides exhibit enhanced chromatographic resolution, improving the separation of positional isomers and co-eluting variants, a key factor in extracting quantitative signals directly from MS1 data. Unlike conventional propionylation, TMA-labeled peptides are compatible with standard proteomics data processing software, requiring no custom computational tools. This robust derivatization workflow positions TMA as a superior alternative for analyzing complex histone modification patterns in biological samples, providing high-resolution, quantitative data essential for epigenetic and chromatin research.

Synthetic Use

Upstream Synthesis Route 1

• 124-63-0
• 75-98-9

• 3282-30-2
• 1538-75-6

Reference: [1] Tetrahedron, 1993, vol. 49, # 8, p. 1535 - 1540

Upstream Synthesis Route 2

• 75-98-9

• 3282-30-2
• 1538-75-6

Reference: [1] Tetrahedron, 1993, vol. 49, # 8, p. 1535 - 1540

Downstream Synthesis Route 1

• 75-85-4
• 1538-75-6

• 38222-83-2
• 108154-12-7
• 108154-13-8

Reference: [1] Bulletin de la Societe Chimique de France, 1986, # 2, p. 307 - 313
[2] Bulletin de la Societe Chimique de France, 1986, # 2, p. 307 - 313

Downstream Synthesis Route 2

• 58-14-0
• 1538-75-6

• 143947-40-4

Reference: [1]Goswami, Shyamaprosad; Adak, Avijit Kumar
[Tetrahedron Letters, 2002, vol. 43, # 46, p. 8371 - 8373]
[2]Taylor, Edward C.; Otiv, S. R.; Durucasu, Inci
[Heterocycles, 1993, vol. 36, # 8, p. 1883 - 1895]
[3]Nasir, M. Sarwar; Karlin, Kenneth D.; Chen, Qin; Zubieta, Jon
[Journal of the American Chemical Society, 1992, vol. 114, # 6, p. 2264 - 2265]

Downstream Synthesis Route 3

• 75-85-4
• 1538-75-6

• 38222-83-2
• 108154-12-7
• 108154-13-8

Reference: [1]Journal of the Chemical Society. Perkin transactions I,1992,p. 1811 - 1820

Downstream Synthesis Route 4

• 4599-47-7
• 1538-75-6

• 110762-12-4

Reference: [1]Bulletin de la Societe Chimique de France,1986,p. 307 - 313
[2]Bulletin de la Societe Chimique de France,1986,p. 307 - 313

* For details of the synthesis route, please refer to the original source to ensure accuracy.