Insulin Degludec Side Chain [L-tBuO-Pal-Glu(OSu)-OtBu]

Insulin Degludec Side Chain [L-tBuO-Pal-Glu(OSu)-OtBu] is a synthetic amino acid derivative essential for the chemical synthesis of Insulin Degludec, a long-acting basal insulin analog. This side chain enables the attachment of a palmitic diacid moiety (with a tert-butyl ether on the omega carbon) to insulin, facilitating multi-hexamer formation for prolonged, stable insulin release. The glutamic acid core links the lipid to insulin; gamma-carboxyl is NHS-activated for conjugation, and the alpha-carboxyl is tert-butyl protected to prevent side reactions.

Appearance

• White to off-white solid or lyophilized powder.

Source

• Synthesized chemically by specialized peptide or custom synthesis labs; not natural.

Molecular Weight and Structure

• Molecular weight approx. 754.0 g/mol (C38H68N2O9).

• Structure includes palmitic diacid chain with tert-butyl ether, glutamic acid with NHS activated gamma-carboxyl and tert-butyl ester protected alpha-carboxyl.

Biological Activity

• Biologically inactive alone; functional when incorporated into insulin.

• Promotes multi-hexamer assembly and extended insulin action.

Purity and Microbial Contamination

• Purity typically >95% to >98% by HPLC; essential for manufacturing quality.

• Very low microbial contamination and endotoxin levels required.

Identity and Quality Control

• Confirmed by MS, NMR spectroscopy.

• Purity via HPLC, water content via Karl Fischer titration, chirality by specific rotation, elemental analysis.

Shelf Life and Storage

 

Applications

• Building block in Insulin Degludec synthesis, enabling site-specific palmitic diacid modification.

• Essential for extended pharmacokinetic profile of basal insulin therapy.

Key Characteristics

• Palmitic diacid for multi-hexamer formation and prolonged action.

• Tert-butyl ether enhances lipophilicity and aggregation control.

• NHS ester enables efficient conjugation.

• Acid-labile tert-butyl ester protection prevents side reactions during synthesis.

• Soluble in DMF, DMSO, acetonitrile.

Citation 

• Jonassen et al. (2012). “Design and development of insulin degludec.” Acta Pharmacologica Sinica, 33(8), 1069-1075.

• Heise et al. (2012). “Ultra-long-acting insulin degludec.” Diabetes Obes Metab, 14(4), 346-352.

• Ribel et al. (2017). “Insulin degludec pharmacology.” Diabetes Res Clin Pract, 125, 16-27.

• Mathieu et al. (2012). “Liraglutide vs insulin glargine in type 1 diabetes.” Lancet, 379(9825), 1484-1491.

• Ratner et al. (2013). “Hypoglycaemia risk with insulin degludec.” Diabetes Obes Metab, 15(2), 175-184.

• Haahr et al. (2013). “PK and PD profiles of insulin degludec.” Diabetes Obes Metab, 15(9), 773-782.

• Owens & Vora (2014). “Insulin degludec overview.” Drugs, 74(12), 1409-1423.

• Novo Nordisk. (2015). Tresiba prescribing info.

• Bailey & Home (2014). “Insulin degludec therapy.” Drugs, 74(17), 1953-1964.

• Jendle et al. (2012). “Insulin degludec reduces nocturnal hypoglycaemia.” Diabetes Obes Metab, 14(2), 146-154.