Connexin-43 (Cx43) is a cardiac connexin involved with gap junction formation, the gap junctions facilitate the exchange of ions and metabolites between cytoplasm and extracellular milieu. Gap19, as selective connexin 43 (Cx43) hemichannel blocker, has cardioprotective properties.
CAT No: R0895
CAS No:1507930-57-5
Synonyms/Alias:Gap19;1507930-57-5;Gap19 TFA;(2S)-6-Amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-5-amino-2-[[(2S)-2,6-diaminohexanoyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]hexanoic acid;Gap19?;HY-P1136;C55H96N14O13;HB5162;AKOS025142096;DA-73656;CS-0028049;
Gap19 is a synthetic peptide specifically designed to target connexin43 (Cx43) hemichannels, a crucial component of gap junctional intercellular communication in various tissues. As a segment derived from the intracellular loop of Cx43, Gap19 exhibits selective inhibition of hemichannel activity without significantly affecting gap junctional coupling. This unique selectivity makes it a valuable molecular tool for dissecting the physiological and pathological roles of Cx43 hemichannels in cellular signaling, tissue homeostasis, and disease models. Its application in experimental systems has advanced the understanding of connexin-mediated pathways and contributed to the exploration of intercellular communication mechanisms in both basic and translational research contexts.
Gap junction research: Gap19 is widely utilized in studies investigating the regulation and function of gap junction channels, particularly those formed by Cx43. By specifically inhibiting hemichannel activity, researchers can differentiate between the roles of hemichannels and fully formed gap junctions in cellular communication. This enables detailed mechanistic studies on the contribution of Cx43 hemichannels to physiological processes such as electrical coupling, metabolic cooperation, and the propagation of signaling molecules between adjacent cells.
Cellular signaling modulation: The peptide serves as a powerful tool to modulate purinergic and calcium signaling pathways that are mediated by Cx43 hemichannels. In various cell types, Cx43 hemichannels facilitate the release of ATP and other signaling molecules into the extracellular environment, influencing autocrine and paracrine signaling cascades. By applying Gap19, researchers can selectively inhibit these processes, allowing for precise analysis of extracellular signaling dynamics and their downstream effects on cell behavior and tissue responses.
Neuroscience and neurobiology research: In neural tissues, Cx43 hemichannels are implicated in the regulation of neuronal-glial interactions and neuroinflammatory responses. Gap19 is employed to study the specific involvement of hemichannels in astrocytic function, synaptic modulation, and neuroprotection. Its use has provided insights into how altered hemichannel activity may contribute to neurodegenerative processes, neural injury, and the maintenance of central nervous system homeostasis, supporting the development of experimental models for neurobiological investigation.
Ischemia and hypoxia modeling: Experimental models of ischemia and hypoxia frequently utilize Gap19 to explore the role of Cx43 hemichannels in cellular injury and tissue damage. Under stress conditions, the opening of hemichannels can exacerbate cell death and inflammation by permitting the uncontrolled exchange of ions and metabolites. By inhibiting hemichannel activity, researchers gain the ability to dissect the pathological mechanisms underlying tissue responses to oxygen deprivation, providing a clearer understanding of cellular resilience and vulnerability.
Peptide structure-function analysis: Gap19 also serves as a reference compound in peptide engineering and structure-function studies focused on connexin proteins. Its defined sequence and selective mode of action make it an ideal template for designing new peptides with tailored properties. Researchers employ it to investigate the structural determinants of connexin channel inhibition, optimize peptide-based modulators, and develop experimental strategies for targeting intercellular communication pathways in vitro and in vivo.
In line with this, we found that Gap19 did not inhibit gap junction coupling in astrocytes as measured with dye transfer assays. At the same time, however, Gap19 strongly inhibited Cx43 hemichannels as exemplified by ATP release and dye uptake assays. Finally, we provide evidence that the TAT version of Gap19 is able to cross the intact blood-brain barrier indicating that this peptide can be used to block astroglial Cx43 hemichannel activity when applied through a vascular route.
The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes
Gap 19 inhibits Cx43 hemichannels without blocking GJ channels or Cx40/pannexin-1 hemichannels. Hemichannel inhibition is due to the binding of Gap19 to the C-terminus (CT) thereby preventing intramolecular CT–CL interactions. The peptide inhibited Cx43 hemichannel unitary currents in both HeLa cells exogenously expressing Cx43 and acutely isolated pig ventricular cardiomyocytes. Treatment with Gap19 prevented metabolic inhibition-enhanced hemichannel openings, protected cardiomyocytes against volume overload and cell death following ischemia/reperfusion in vitro and modestly decreased the infarct size after myocardial ischemia/reperfusion in mice in vivo.
Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury
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