A potent and specific KV1.3 channel blocker, and exhibits no effect at calcium-activated channels. Margatoxin can reduces VEGF-induced transmembrane calcium influxes and nitric oxide production in human endothelial cells.
CAT No: R0995
CAS No:145808-47-5
Synonyms/Alias:Margatoxin;145808-47-5;6197NL836C;UNII-6197NL836C;potassium channel toxin alpha-KTx 2.2;MARGATOXIN [MI];DTXSID90897082;HB1083;C178H286N52O50S7;DA-75321;FM108623;H-Thr-Ile-Ile-Asn-Val-Lys-Cys-Thr-Ser-Pro-Lys-Gln-Cys-Leu-Pro-Pro-Cys-Lys-Ala-Gln-Phe-Gly-Gln-Ser-Ala-Gly-Ala-Lys-Cys-Met -Asn-Gly-L ys-Cys-Lys-Cys-Tyr-Pro-His-OH; H-TIINVKCTSPKQCLPPCKAQFGQSAGAKCMNGKCKCYPH-OH;THR-ILE-ILE-ASN-VAL-LYS-CYS-THR-SER-PRO-LYS-GLN-CYS-LEU-PRO-PRO-CYS-LYS-ALA-GLN-PHE-GLY-GLN-SER-ALA-GLY-ALA-LYS-CYS-MET-ASN-GLY-LYS-CYS-LYS-CYS-TYR-PRO-HIS, CYCLIC (7->29),(13->34),(17->36)-TRIS(DISULFIDE);
Margatoxin is a potent peptide toxin originally isolated from the venom of the scorpion Centruroides margaritatus, and is recognized for its high specificity as a voltage-gated potassium channel inhibitor, particularly targeting the Kv1.3 subtype. As a member of the scorpion toxin family, margatoxin exhibits a well-defined disulfide-rich structure, conferring both stability and selectivity in its interactions with ion channel proteins. Its unique ability to modulate the function of Kv1.3 channels has positioned it as a valuable molecular tool in neurophysiological research and ion channel pharmacology. Researchers employ margatoxin to dissect the roles of potassium channels in cellular signaling, immune responses, and membrane excitability, making it a critical reagent for advancing our understanding of channelopathies and electrophysiological processes.
Ion Channel Research: Margatoxin is widely utilized in fundamental studies of voltage-gated potassium channels, particularly for its nanomolar affinity for Kv1.3 and related subtypes. By selectively inhibiting these channels, the peptide enables precise functional dissection of their roles in neuronal excitability, synaptic transmission, and action potential shaping. Its application in patch-clamp electrophysiology and related assays allows investigators to delineate the contributions of specific potassium channels to overall membrane dynamics, facilitating the exploration of ion channel diversity and regulation in excitable tissues.
Immunology Studies: The Kv1.3 channel, a primary target of margatoxin, plays a pivotal role in the activation and proliferation of T lymphocytes. Researchers leverage the peptide's selectivity to investigate the mechanistic basis of immune cell signaling, calcium influx, and cytokine production. By employing margatoxin in vitro, scientists can modulate immune cell function and gain insights into the molecular pathways governing immune responses, autoimmunity, and inflammation, thereby expanding the understanding of immunological signaling networks.
Pharmacological Screening: Margatoxin serves as a reference inhibitor in the development and validation of new potassium channel modulators. Its well-characterized binding profile and reproducible inhibitory effects make it an essential control compound in high-throughput screening assays and structure-activity relationship studies. Through competitive binding and functional assays, researchers use this peptide to benchmark the efficacy and selectivity of novel small molecules or biologics targeting Kv1.3 and related channels, supporting the advancement of ion channel drug discovery.
Neuroscience Investigations: The modulation of neuronal potassium channels by margatoxin provides critical insights into the regulation of synaptic plasticity, neurotransmitter release, and network oscillations. By applying the peptide in neuronal cultures or brain slice preparations, neuroscientists can probe the physiological and pathophysiological roles of Kv1.3 channels within central and peripheral nervous systems. This approach facilitates the elucidation of mechanisms underlying learning, memory, and neurological disorders associated with altered potassium channel function.
Peptide Structure-Function Analysis: The disulfide-rich architecture of margatoxin, coupled with its high-affinity binding to Kv1.3 channels, makes it an exemplary model for structure-activity relationship studies of peptide toxins. Researchers utilize the peptide in mutagenesis experiments, NMR spectroscopy, and computational modeling to unravel the molecular determinants of channel recognition, binding kinetics, and conformational stability. These investigations not only deepen the understanding of peptide-channel interactions but also inform the rational design of synthetic analogs and engineered peptides with tailored pharmacological properties.
When MgTx was isolated and its high affinity interaction with Kv1.3 was precisely characterized it was only tested on a limited number of channels excluding Kv1.1, Kv1.2 and Kv1.4 channels, those with high sequence homology to Kv1.3. Later the authors who described MgTx and other workgroups refer to the peptide as potent blocker of Kv1.1, Kv1.2 and Kv1.3 channels, whereas the references do not describe or contain any information about the interaction of MgTx and the Kv1.1 or Kv1.2 channels. Without the precise characterization of the selectivity profile of MgTx, results from radioactively labeled MgTx binding assays, observed potassium current block or other biological effects of the peptide may not be considered as a direct proof of Kv1.3 expression. In addition, MgTx shares high sequence homology with other scorpion peptides that block both Kv1.3 and Kv1.2 channels with high affinity (Noxiustoxin, Css20) suggesting that MgTx may be a non-selective peptide as well.
Margatoxin is a non-selective inhibitor of human Kv1.3 K+channels
Margatoxin (MgTX), a 39-amino acid peptide from Centruroides margaritatus, is a potent inhibitor of lymphocyte KV channels. The binding of monoiodotyrosinyl margatoxin ([125I]MgTX) to plasma membranes prepared from either Jurkat cells, a human leukemic T cell line, or CHO cells stably transfected with the Shaker-type voltage-gated K+ channel, KV1.3, has been used to investigate the properties of lymphocyte KVchannels. These data were compared with [125I]MgTX binding to heterotetrameric KV channels in rat brain synaptic plasma membranes.
Margatoxin Binds to a Homomultimer of KV1.3 Channels in Jurkat Cells. Comparison with KV1.3 Expressed in CHO Cells
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