[Ala11,D-Leu15]-Orexin B

Product Name:[Ala11,D-Leu15]-Orexin B

CAS No:532932-99-3

Purity:95%

Molar Mass:2857.26

Chemical Formula:C120H206N44O35S

Storage:Store at -20 degrees Celsius

Sequence:RSGPPGLQGRAQRLLQASGNHAAGILTM-NH2

Target:orexin-2 receptor (OX2) agonist

Application:

[Ala¹¹,D-Leu¹⁵]-Orexin B is a synthetic analog of the neuropeptide Orexin B, modified to enhance stability and alter receptor binding properties. This analog features substitutions at positions 11 and 15, where alanine (Ala) and D-leucine (D-Leu) replace the native residues. [Ala¹¹,D-Leu¹⁵]-Orexin B is used extensively in research to explore the role of orexin signaling in regulating sleep-wake cycles, appetite, and energy balance. By studying this analog, researchers gain insights into the potential therapeutic applications of targeting orexin receptors, particularly for treating sleep disorders, obesity, and metabolic dysfunctions linked to orexin pathways.

Current Research:

[Ala¹¹,D-Leu¹⁵]-Orexin B is a synthetic analog of the endogenous neuropeptide Orexin B, engineered to investigate the structure-activity relationships and receptor selectivity of orexin peptides. In this analog, the eleventh amino acid is substituted with alanine, and the fifteenth position incorporates D-leucine. These modifications are designed to alter the peptide's conformation and receptor interaction profiles, providing insights into the functional domains critical for receptor binding and activation.

Structural Modifications and Implications

The substitution of the eleventh residue with alanine simplifies the side chain at this position, potentially affecting the peptide's secondary structure and its interaction with orexin receptors. Incorporating D-leucine at position fifteen introduces a stereochemical alteration that can influence the peptide's stability and receptor selectivity. These strategic modifications are utilized to dissect the roles of specific residues in receptor binding affinity and signaling efficacy.

Receptor Selectivity and Biological Activity

Orexin peptides, including Orexin B, interact with two G protein-coupled receptors: OX₁R and OX₂R. Modifications in [Ala¹¹,D-Leu¹⁵]-Orexin B are intended to study changes in binding affinities and activation profiles toward these receptors. Such analogs are instrumental in identifying receptor-specific interactions and understanding the molecular determinants of receptor selectivity.

Research Applications

This analog serves as a valuable tool in neuropharmacological research, particularly in:

Elucidating the structural requirements for orexin receptor activation and signaling pathways.

Investigating the physiological roles of orexin receptors in processes such as sleep-wake regulation, appetite control, and energy homeostasis.

Developing therapeutic agents targeting orexin receptors for conditions like narcolepsy, insomnia, and metabolic disorders.

Conclusion

[Ala¹¹,D-Leu¹⁵]-Orexin B exemplifies the use of peptide engineering to probe the intricacies of receptor-ligand interactions within the orexin system. By providing insights into the structural elements critical for receptor specificity and function, this analog contributes to the advancement of targeted therapies modulating orexin receptor activity.

Reference:

Asahi, S., Egashira, S. I., Matsuda, M., Iwaasa, H., Kanatani, A., Ohkubo, M., ... & Morishima, H. (2003). Development of an orexin-2 receptor selective agonist,[Ala11, D-Leu15] orexin-B. Bioorganic & medicinal chemistry letters, 13(1), 111-113.