Isotope labelled Linaclotide. Linaclotide is a 14-amino acid peptide indicated for the treatment of adults with CC and IBS-C; agonist of guanylate cyclase C
CAT No: 10-101-194
CAS No:851199-59-2 (non-d)
Synonyms/Alias:L-Cysteinyl-L-cysteinyl-L-α-glutamyl-L-tyrosyl-L-cysteinyl-L-cysteinyl-L-asparaginyl-L-prolyl-L-alanyl-d4-L-cysteinyl-L-threonylglycyl-L-cysteinyl-L-tyrosine Cyclic (1→6),(2→10),(5→13)-Tris(disulfide); 11: PN: WO2008151257 SEQID: 55 claimed protein-d4; 13: PN: WO2008151257 SEQID: 57 Claimed Protein-d4; 2074: PN: US20090062207 SEQID: 3 Claimed Protein-d4; 40: PN: WO2010065751 SEQID: 55 Claimed Protein-d4; 42: PN: WO2010065751 SEQID: 57 claimed protein-d4; 55: PN: US20100152118 SEQID: 55 Claimed Protein-d4; 55: PN: WO2011069038 SEQID: 55 Claimed Sequence-d4; 55: PN: WO2012037380 SEQID: 55 Unclaimed Protein-d4; 57: PN: WO2011069038 SEQID: 57 Claimed Sequence-d4; 57: PN: WO2012037380 SEQID: 57 Claimed Protein-d4
Linaclotide D4 is a stable isotope-labeled peptide derivative of linaclotide, a synthetic 14-amino acid peptide and guanylate cyclase-C (GC-C) agonist. As a deuterium-labeled analog, Linaclotide D4 is distinguished by the incorporation of four deuterium atoms, which makes it highly valuable for advanced analytical and pharmacokinetic research. Its molecular structure closely mirrors that of native linaclotide, allowing it to serve as an internal standard or tracer in mass spectrometry-based studies while preserving the essential biochemical and functional properties of the parent peptide. The unique isotopic labeling enhances detection sensitivity and quantification accuracy, making Linaclotide D4 an indispensable tool for peptide research and method development in complex biological matrices.
Analytical standardization: Linaclotide D4 is extensively used as an internal standard in quantitative bioanalytical assays, particularly those utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS). The incorporation of deuterium atoms provides a distinct mass shift, enabling precise differentiation from endogenous or unlabeled linaclotide during sample analysis. This property allows for highly accurate quantification of linaclotide concentrations in biological fluids, supporting pharmacokinetic profiling, metabolic stability studies, and bioequivalence assessments in preclinical research settings.
Peptide metabolism studies: The deuterium-labeled structure of Linaclotide D4 makes it a valuable probe for elucidating peptide degradation pathways and metabolic fate. By tracking the labeled peptide in in vitro or in vivo systems, researchers can gain detailed insights into the enzymatic processes, stability, and transformation products associated with linaclotide. This application is crucial for understanding peptide pharmacokinetics, optimizing peptide drug design, and evaluating the impact of metabolic modifications on biological activity.
Peptide synthesis validation: In peptide manufacturing and synthetic chemistry laboratories, Linaclotide D4 serves as a reference material for validating the identity and purity of synthesized linaclotide batches. Its isotopic signature enables unambiguous confirmation of synthetic yield and product integrity through co-elution and mass spectral comparison. This application streamlines quality control processes and ensures reproducibility in peptide production workflows, which is essential for research and development environments.
Method development and optimization: The availability of a stable isotope-labeled linaclotide analog supports the development and optimization of robust analytical methods for peptide quantification. Linaclotide D4 is instrumental in establishing assay sensitivity, linearity, and recovery in complex sample matrices such as plasma, serum, or tissue extracts. Its use facilitates the validation of extraction protocols, calibration curves, and instrument performance, thereby improving the reliability of peptide analysis in both academic and industrial laboratories.
Receptor binding and functional studies: Although primarily applied as an analytical tool, Linaclotide D4 can also be utilized in receptor binding assays and functional studies to investigate the interaction of linaclotide analogs with GC-C or related signaling pathways. The deuterium label allows for selective monitoring in mixed-ligand experiments, supporting mechanistic studies of peptide-receptor engagement, downstream signaling events, and structure-activity relationships. These insights contribute to a deeper understanding of GC-C agonist biology and inform the rational design of novel peptide therapeutics.
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