(D-His1)-Liraglutide - GLP1 receptor agonist

(D-His1)-Liraglutide is a high-quality liraglutide impurity, in which the N-terminal L-histidine is replaced with its D-enantiomer. Retaining the C16 fatty acid chain at Lys26, the peptide preserves liraglutide’s parent structure but lacks pharmacological activity. It serves as a fully characterized reference standard for analytical method development, method validation (AMV), and quality control (QC) during liraglutide manufacturing, ensuring compliance with regulatory guidelines.

For research use only, do not use in humans!

Produced by JPT Peptide Technologies, a leader in custom peptide synthesis and diabetes reagents.

(D-His1)-Liraglutide - GLP1 receptor agonist - Specifications

• Peptide sequence: H-hAEGTFTSDVSSYLEGQAA-Lys(Palmitoyl-gammaGlu)-EFIAWLVRGRG-OH
• Amount: 0.5 mg net (50 x 10 µg) (AAA)
• Purity: >95% (HPLC-MS)
• Counterion: TFA
• Delivery Format: Freeze-dried in plastic vial
• Chemical formula: C172H265N43O51
• MW (average): 3751.26
• Application(s): Diabetes research
• Condition(s)/Topic(s): Diabetes
• Standard Delivery Time: 2-5 days
• SMILES: N[C@H](CC1=CNC=N1)C(N[C@@H](C)C(N[C@@H](CCC(O)=O)C(NCC(N[C@@H]([C@@H](C)O)C(N[C@@H](CC2=CC=CC=C2)C(N[C@@H]([C@@H](C)O)C(N[C@H](C(N[C@@H](CC(O)=O)C(N[C@@H](C(C)C)C(N[C@@H](CO)C(N[C@H](C(N[C@@H](CC3=CC=C(O)C=C3)C(N[C@@H](CC(C)C)C(N[C@@H](CCC(O)=O)C(NCC(N[C@@H](CCC(N)=O)C(N[C@@H](C)C(N[C@@H](C)C(N[C@@H](CCCCNC(CC[C@@H](C(O)=O)NC(CCCCCCCCCCCCCCC)=O)=O)C(N[C@@H](CCC(O)=O)C(N[C@@H](CC4=CC=CC=C4)C(N[C@@H]([C@@H](C)CC)C(N[C@@H](C)C(N[C@@H](CC5=CNC6=C5C=CC=C6)C(N[C@@H](CC(C)C)C(N[C@@H](C(C)C)C(N[C@@H](CCCNC(N)=N)C(NCC(N[C@@H](CCCNC(N)=N)C(NCC(O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)CO)=O)=O)=O)=O)CO)=O)=O)=O)=O)=O)=O)=O

Structure of (D-His1)-Liraglutide Peptide

(D-His1)-Liraglutide is a 31-amino-acid peptide analogue of liraglutide and, therefore, a synthetic GLP-1 receptor agonist corresponding to residues 7-37 of human glucagon-like peptide-1. It retains liraglutide’s overall structure, including the C16 palmitic acid side chain attached via a γ-glutamic acid spacer to Lys26, which promotes albumin binding and prolongs plasma half-life in the parent drug.

However, in D-His(1) Liraglutide, the N-terminal L-histidine is substituted with its D-enantiomer, introducing an inversion of chirality at position 1 that alters the peptide’s three-dimensional orientation and biochemical properties. This stereochemical change preserves the overall molecular framework but abolishes receptor activation, rendering the peptide pharmacologically inactive while maintaining analytical comparability to liraglutide.

JPT Peptide Technologies offers also customized variants tailored to your research needs. More information is available at our Custom Peptide Synthesis services.

Research Areas and Applications of D-His(1) Liraglutide

• Detection of stereochemical variants: Explored for its potential in identifying D/L-isomeric impurities formed during liraglutide synthesis to ensure the peptide’s stereochemical purity.
• Analytical method development studies: Investigated for its application in HPLC and LC-MS method development for detecting stereochemical impurities in liraglutide.
• Quality control (QC) research: Examined as a reference impurity standard in studies assessing purity, identity, and batch-to-batch consistency during liraglutide manufacturing.
• Stability and process validation research: Utilized in studies exploring peptide stability, process validation, and monitoring of structural integrity under various storage and manufacturing conditions.
• Regulatory compliance research: Studied for its relevance in meeting ICH and GMP requirements for impurity profiling and characterization, supporting Abbreviated New Drug Applications (ANDA) and dossier submissions.
• Pharmacopeial traceability exploration: Investigated for its potential role as a reference standard traceable to pharmacopeial specifications (e.g., USP or EP), supporting method standardization and quality assurance.

Key Concepts

What is Liraglutide?

Liraglutide, also known as the active ingredient in Victoza® and Saxenda®, is a synthetic GLP-1 receptor agonist that mimics human glucagon-like peptide-1 (7-37), a hormone regulating glucose metabolism and appetite. The 31-amino-acid peptide is modified with a C16 palmitic acid chain attached via a γ-glutamic acid spacer to Lys26. This structural alteration enhances albumin binding and extends its plasma half-life (˜13 hours), allowing once-daily administration of liraglutide-based drugs.

Liraglutide stimulates insulin secretion and suppresses glucagon release in a glucose-dependent manner after meals, providing prolonged activity compared with endogenous GLP-1. It also slows gastric emptying, reduces appetite, and supports weight loss, making it effective in treating type 2 diabetes and obesity while lowering related cardiovascular risks. Due to its structural complexity, the manufacture and quality control of liraglutide rely on precise analytical standards such as (D-His1)-Liraglutide, which enable the detection of stereochemical impurities and ensure product purity.

What is an Enantiomer?

An enantiomer is one of two molecules that share the same molecular formula, mass, and atom connectivity, yet differ in their three-dimensional arrangement of atoms, forming mirror-image structures that cannot be aligned perfectly. This property, known as chirality, arises when a molecule contains a chiral center, typically a carbon atom bonded to four different groups.

Although enantiomers are chemically identical in composition, they can exhibit different biological or pharmacological behavior, since many enzymes and receptors recognize only one spatial configuration. In peptide chemistry, substituting an L-amino acid (the naturally occurring, left-oriented configuration found in proteins) with its D-enantiomer (the mirror-image, right-oriented configuration) alters the molecule’s chirality and can influence its conformation, stability, and biological activity.

What are Analytical Reference Standards?

Analytical reference standards are highly purified, well-characterized compounds used to confirm the identity, purity, and concentration of substances throughout chemical synthesis, formulation, and quality control. They act as reliable benchmarks in analytical techniques such as HPLC and LC-MS, ensuring that test results remain accurate, reproducible, and traceable.

In the analysis of complex molecules like peptides, these standards are indispensable for detecting impurities and ensuring the quality and consistency of manufacturing processes. For instance, (D-His1)-Liraglutide serves as a reference material for monitoring stereochemical integrity during liraglutide production.

JPT’s Diabetes Peptide%3b GLP-1 receptor agonists

Glucagon-like Peptide 1 (GLP-1) and other GLP-1 receptor agonists have proven to be an effective treatment of Type 2 diabetes and obesity, offering significant benefits. They improve glycemic control by enhancing insulin secretion in response to elevated blood glucose levels; help reduce glucagon levels, further supporting blood sugar regulation; and slow gastric emptying, leading to weight loss, which is beneficial for diabetic patients who are obese. JPT Peptide Technologies has substantial, long-standing expertise in providing peptides in all formats, scales and modifications to the global scientific community. All our catalog peptides are provided with HPLC-MS analyses to confirm the identity and demonstrate the high quality of our peptides.

• All peptides are made in Germany
• Bulk orders or custom peptide synthesis upon request
• Provision of freeze-dried aliquots for enhanced stability
• Proven track record
• Need the conjugated or modified peptide? Contact us!