Lipidated connexin mimetic peptides potently inhibit gap junction-mediated Ca2+-wave propagation.

@article{Cotter2018LipidatedCM,
  title={Lipidated connexin mimetic peptides potently inhibit gap junction-mediated Ca2+-wave propagation.},
  author={Mary Lou Cotter and Scott A. Boitano and Josef Vagner and Janis M Burt},
  journal={American journal of physiology. Cell physiology},
  year={2018},
  volume={315 2},
  pages={
          C141-C154
        }
}
Connexin (Cx) mimetic peptides (e.g., Gap27: SRPTEKTIFII; Peptide5: VDCFLSRPTEKT) reversibly inhibit hemichannel (HCh) and gap junction channel (GJCh) function in a concentration- and time-dependent manner (HCh: ~5 µM, <1 h; GJCh: ~100 µM, > 1 h). We hypothesized that addition of a hexadecyl tail to SRPTEKT (SRPTEKT- Hdc) would improve its ability to concentrate in the plasma membrane and consequently increase its inhibitory efficacy. We show that SRPTEKT- Hdc inhibited intercellular Ca2+-wave… 
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The lipidated connexin mimetic peptide, SRPTEKT-Hdc, is a potent inhibitor of Cx43 channels with specificity for the pS368 phospho-isoform.
TLDR
Adding a hexadecyl (Hdc) lipid tail to the conserved SRPTEKT peptide sequence results in a novel, highly efficacious and potent inhibitor of mechanically-induced Ca2+-wave propagation and dye uptake in Madin-Darby canine kidney cells expressing rCx43 (MDCK43).
Therapeutic Targeting of Connexin Channels: New Views and Challenges.
TLDR
A critical overview on the use of connexin-targeting peptides, in particular targeting Cx43, is provided, with a special focus on the remaining questions and hurdles to be taken in the research field of con Nexin channels.
Mechanisms of Connexin Mimetic Peptides
Gap junctions (GJ) and connexins play integral roles in cellular physiology and have been found to be involved in multiple pathophysiological states from cancer to cardiovascular disease. Studies…
Mechanisms of Connexin Regulating Peptides
TLDR
This overview of published connexin targeting peptides, their reported mechanisms of action, and the potential for these molecules in the treatment of disease is discussed.
Synthesis and biological evaluation of S-lipidated lipopeptides of a connexin 43 channel inhibitory peptide.
The synthesis and biological activity of 42 novel S-lipidated analogues of a connexin 43 channel inhibitory Peptide5 is described. Unmodified Peptide5 moderates hemichannels and gap junctions that…
Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine
TLDR
Preclinical and clinical data available on short mimetic peptides based on, or directly targeting, Cx43, with focus on their potential for treating heart disease are surveyed and problems that have caused reluctance within the pharmaceutical industry to translate peptidic therapeutics to the clinic are discussed.
Targeting gap junction in epilepsy: Perspectives and challenges.
TLDR
Targeting GJs is likely to be served as a novel therapeutic approach on epileptic patients and exert potent curative potential on epilepsy in vivo or in vitro.
Cardiac Conduction Velocity, Remodeling and Arrhythmogenesis
TLDR
Methods to measure cardiac CV in vivo and ex vivo are examined, underlying determinants of CV are discussed, and how pathological variations alter CV is addressed, potentially increasing arrhythmogenic risk.

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