Non-competitive NMDA receptor antagonist (IC50 = 0.4 μM) that inhibits Ca2+ influx and glutamate-induced toxicity in central nervous system neurons.
Conantokin-T is a peptide neurotoxin originally isolated from the venom of the marine cone snail Conus tulipa. As a member of the conantokin family, it is characterized by its unique gamma-carboxyglutamate (Gla) residues, which confer calcium-dependent conformational properties and enable specific interactions with ion channels. Conantokin-T acts as a potent and selective antagonist of N-methyl-D-aspartate (NMDA) receptors, particularly those containing the NR2B subunit, making it a valuable molecular tool in neuropharmacology and synaptic physiology research. Its distinct structural and functional properties have positioned it as a model compound for studying peptide-receptor interactions, ion channel modulation, and the biochemical consequences of post-translational modifications in peptides.
Neuropharmacology research: As a selective NMDA receptor antagonist, conantokin-T is widely employed to dissect the physiological and pathological roles of NMDA receptor subtypes in the central nervous system. Its ability to modulate excitatory neurotransmission with high specificity allows researchers to explore synaptic plasticity, excitotoxicity, and the molecular underpinnings of learning and memory. By selectively targeting NR2B-containing NMDA receptors, the peptide provides a means to differentiate receptor subtype contributions in neuronal signaling pathways, offering insights into the complex dynamics of glutamatergic neurotransmission.
Ion channel studies: The unique calcium-dependent folding and activity of conantokin-T, conferred by its Gla residues, make it an important tool for investigating the structural and functional relationships between peptides and ion channels. Researchers use it to probe the mechanisms of peptide-induced ion channel modulation, particularly in the context of ligand-gated ion channels such as NMDA receptors. Its selective binding and antagonism facilitate detailed studies of ion channel gating, allosteric regulation, and the structural determinants of channel specificity.
Peptide structure-function analysis: The presence of post-translationally modified amino acids in conantokin-T, especially gamma-carboxyglutamate, provides a platform for exploring the impact of such modifications on peptide conformation, stability, and receptor interaction. Synthetic and analytical studies use the peptide as a model to elucidate how Gla residues influence helical structure, calcium binding, and bioactivity. This research advances understanding of the structure-activity relationships in bioactive peptides and informs the rational design of novel peptide-based modulators.
Drug discovery and lead optimization: Due to its potent and selective action on NMDA receptor subtypes, conantokin-T serves as a valuable lead compound in the development of new neuroactive agents. Medicinal chemists utilize it as a template for designing analogs with improved stability, selectivity, or pharmacokinetic properties. By systematically modifying its sequence or post-translational modifications, researchers can generate libraries of peptide derivatives to screen for novel modulators of glutamatergic signaling, supporting early-stage drug discovery efforts in neurobiology.
Analytical and assay development: The well-characterized pharmacological profile and receptor selectivity of conantokin-T make it a useful reference compound in the development and validation of bioassays targeting NMDA receptors. It is frequently employed as a positive control or benchmark in high-throughput screening assays, receptor binding studies, and functional electrophysiological recordings. Its reproducible activity and specificity help ensure assay reliability and facilitate the quantitative assessment of novel NMDA receptor ligands in research and industrial settings.
Conatokins-T, a 21-animo acid peptide which induces sleep-like symptoms in young mice was purified from the venom of the fish-hunting cone snail, Conus tulipa. The amino acid sequence of the peptide was determined and verified by chemical synthesis. The peptide has 4 residues of the modified amino acid, ycarboxyglutamate (Gla). The sequence of the peptide is: Gly-Glu-Gla-GIa-Tyr-Gln-Lys-Met-Leu-Gla-AsnLeu-Arg-Gla-Ala-Glu-Val-Lys-Lys-Asn-Ala-NHz. Conantokin-T inhibits N-methyl-D-aspartate (NMDA) receptor-mediated calcium influx in central nervous system neurons. This observation suggests that like conantokin-G (a homologous Conus peptide with recently identified NMDA antagonist activity) conantokin-T has NMDA antagonist activity. A sequence comparison of conantokins-T and -G identifies the 4 GIa residues and the N-terminal dipeptide sequence as potential key elements for the biological activity of this peptide.
Conantokin-T. A gamma-carboxyglutamate containing peptide with N-methyl-d-aspartate antagonist activity
Conantokin-T (Con-T), which contains four Gla residues, is a 21-residue peptide isolated from C. tulipa venoms, sharing about 40% sequence homology with Con-G. Both Con-G and Con-T in-duce a sleeping effect in young mice but hyperactive behaviour in old mice when administered by intracranial injection.
Role of modified glutamic acid in the helical structure of conantokin-T
4. Peptides as Active Ingredients: A Challenge for Cosmeceutical Industry
5. Implications of ligand-receptor binding kinetics on GLP-1R signalling
If you have any peptide synthesis requirement in mind, please do not hesitate to contact us at . We will endeavor to provide highly satisfying products and services.
Creative Peptides is a trusted CDMO partner specializing in high-quality peptide synthesis, conjugation, and manufacturing under strict cGMP compliance. With advanced technology platforms and a team of experienced scientists, we deliver tailored peptide solutions to support drug discovery, clinical development, and cosmetic innovation worldwide.
From custom peptide synthesis to complex peptide-drug conjugates, we provide flexible, end-to-end services designed to accelerate timelines and ensure regulatory excellence. Our commitment to quality, reliability, and innovation has made us a preferred partner across the pharmaceutical, biotechnology, and personal care industries.
Read More