GeX-2 peptide

GeX-2 peptide

• Handling and Storage of Synthetic Peptides
• Material Safety Data Sheets (MSDS)

H-GRYRSPYDRRRRYRRITD-NH2

H-Gly-Arg-Tyr-Arg-Ser-Pro-Tyr-Asp-Arg-Arg-Arg-Arg-Tyr-Arg-Arg-Ile-Thr-Asp-NH2

18

95.61%

C₁₀₃H₁₆₉N₄₃O₂₇

2441.71

Synthetic

Powder

Severe pain significantly impacts both the physical and mental well-being of patients, underscoring the urgent need for the development of nonopioid analgesics to address medical requirements. GeX-2, an 18-amino acid short peptide derived from αO-conotoxin through disulfide-bond deletion and sequence truncation, has shown promise in this regard. GeX-2 maintains the efficacy of its parent peptide at the human α9α10 nAChR and demonstrates potent inhibitory effects on CaV2.2 channels by activating the GABAB receptor (GABABR). Notably, GeX-2 has been found to significantly alleviate pain in rat models of chronic constriction injury. Its dual inhibition of α9α10 nAChRs and CaV2.2 channels is believed to synergistically contribute to its potent analgesic properties. Findings from site-directed mutagenesis assays and computational modeling indicate that GeX-2 exhibits a preference for interacting with the α10(+)α10(−) binding site of α9α10 nAChR and has a favorable binding affinity to the top region of the GABABR2 subunit. This study provides valuable insights into the molecular mechanisms of GeX-2 action, highlighting its potential as an innovative nonopioid analgesic option.

Normally, this peptide will be delivered in lyophilized form and should be stored in a freezer at or below -20 °C. For more details, please refer to the manual:Handling and Storage of Synthetic Peptides

• Li X, Tae HS, Chen S, Yousuf A, Huang L, Zhang J, Jiang T, Adams DJ, Yu R. Dual Antagonism of α9α10 nAChR and GABAB Receptor-Coupled CaV2.2 Channels by an Analgesic αO-Conotoxin Analogue. J Med Chem. 2024 Jan 25;67(2):971-987. doi: 10.1021/acs.jmedchem.3c00979. Epub 2024 Jan 13. PMID: 38217860.

Trifluoroacetic acid (TFA) has a significant impact on peptides due to its role in the peptide synthesis process.

TFA is essential for the protonation of peptides that lack basic amino acids such as Arginine (Arg), Histidine (His), and Lysine (Lys), or ones that have blocked N-termini. As a result, peptides often contain TFA salts in the final product.

TFA residues, when present in custom peptides, can cause unpredictable fluctuations in experimental data. At a nanomolar (nM) level, TFA can influence cell experiments, hindering cell growth at low concentrations (as low as 10 nM) and promoting it at higher doses (0.5–7.0 mM). It can also serve as an allosteric regulator on the GlyR of glycine receptors, thereby increasing receptor activity at lower glycine concentrations.

In an in vivo setting, TFA can trifluoroacetylate amino groups in proteins and phospholipids, inducing potentially unwanted antibody responses. Moreover, TFA can impact structure studies as it affects spectrum absorption.