Nα-Palmitoyl-(D)-glutamic acid-γ-succinimidyl-α-tert-butyl ester [D-Pal-Glu(OSu)-OtBu]

Nα-Palmitoyl-(D)-glutamic acid-γ-succinimidyl-α-tert-butyl ester, abbreviated as D-Pal-Glu(OSu)-OtBu, is a synthetically derived building block used for lipidating peptides, proteins, or other molecules. It combines palmitic acid (a saturated fatty acid) with D-glutamic acid and an N-hydroxysuccinimide (NHS) ester (OSu). The palmitic acid imparts lipophilicity for membrane insertion, while the NHS ester provides a reactive site for conjugation to primary amines. The tert-butyl ester (OtBu) protects one glutamic acid carboxyl group, allowing selective deprotection and further modifications. The presence of D-glutamic acid may enhance enzymatic stability and alter recognition in biological systems. Applications include membrane-anchored peptide synthesis, liposomal formulation, protein modification, and surface hydrophobic modification.

Appearance

• White to off-white solid, potentially waxy due to the palmitic acid chain.

Source

• Synthesized chemically; not found in nature.

• Available from specialized chemical and bioconjugation suppliers.

Molecular Weight and Structure

• Approximate molecular weight: 566.7 g/mol (C29H50N2O8).

• Structure: Palmitic acid attached to the α-amino group of D-glutamic acid; the γ-carboxyl of glutamic acid is protected as a tert-butyl ester, and the other carboxyl group is activated as an NHS ester.

Biological Activity

• Biologically inert alone; activity depends on incorporated molecules.

• Lipophilic chain enables membrane insertion, influencing localization and activity of conjugated biomolecules.

• NHS ester facilitates covalent conjugation to biomolecules.

• The D-amino acid configuration may improve enzymatic stability.

Purity and Microbial Contamination

• Purity: Typically ≥ 95% (HPLC).

• Microbial contamination minimal or absent; suppliers provide COAs.

• Tested with endotoxin (LAL assay) and sterility tests.

Identity and Quality Control

• Mass spectrometry confirms molecular weight.

• NMR (¹H, ¹³C) confirms structure.

• IR spectroscopy confirms functional groups (ester carbonyls, amides).

• HPLC evaluates purity.

• Optical rotation measurement confirms D-configuration.

• Amine quantification confirms NHS ester reactivity.

Shelf Life and Storage

Application

• Lipopeptide synthesis (membrane anchoring).

• Protein lipid modification.

• Component in liposomal drug formulations.

• Surface modification with hydrophobic coatings.

• Bioconjugation reagent for primary amine coupling.

Key Characteristics

• Lipophilic palmitoyl chain facilitates membrane insertion.

• NHS ester reacts readily with primary amines.

• OtBu protects glutamic acid for selective deprotection.

• D-glutamic acid may impart enhanced stability.

• Soluble in organic solvents including chloroform, dichloromethane, and DMSO.

Citation 

• NHS ester lipid conjugation chemistry and applications:
  https://pubmed.ncbi.nlm.nih.gov/30613757/

• Bioconjugation strategies using N-hydroxysuccinimide esters:
  https://pubmed.ncbi.nlm.nih.gov/20420327/

• Palmitoylation of peptides and proteins in drug delivery:
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6653962/

• Lipidated peptides and their use in liposomal formulations:
  https://pubmed.ncbi.nlm.nih.gov/30817167/

• Self-assembling lipopeptides with NHS ester modifications:
  https://pubmed.ncbi.nlm.nih.gov/29395641/

• Synthetic lipopeptides containing D-amino acids for stability:
  https://doi.org/10.1002/anie.202001378

• N-hydroxysuccinimide ester reagents in site-specific protein modification:
  https://pubmed.ncbi.nlm.nih.gov/29454358/

• Chemical structure and synthesis of protected glutamic acid derivatives:
  https://pubchem.ncbi.nlm.nih.gov/compound/5386443

• Patents on lipopeptide therapeutics and conjugation chemistry:
  https://patents.google.com/patent/US20170268536A1/en

• Review on fatty acylation and lipid modification of peptides:
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357263/