Gap 27 is a peptide (Ser-Arg-Pro-Thr-Glu-Lys-Thr-Ile-Phe-Ile-Ile) derived from connexin43 (Cx43) and is a selective gap junction blocker[1, 2]. Gap 27 specifically acts on this protein by mimicking a part of the Cx43 structure, thereby inhibiting intercellular communication mediated by Cx43[3]. Gap junctions are channel structures on adjacent cell membranes that allow small molecules to be directly transferred between cells and are essential for coordinating cell group activities[4].
In vitro, Gap 27 (500µM) treatment of rat osteoclasts cultured on bovine bone slices for 48h significantly reduced the survival rate of osteoclasts and the number of TRAP-positive mononuclear and multinuclear rat osteoclasts[5]. Gap 27 (0.1mM) treatment of primary human corneal epithelial cells (HCEC) enhanced wound closure of HCEC in vitro[6].
In vivo, Gap 27 (1µg/kg) treated with osmotic micropumps for 4 weeks in rats with an arteriovenous fistula model (AV-Shunt) significantly slowed the progression of cardiac function deterioration and significantly improved cardiac function in rats[7].
References:
[1] De Vuyst E, Boengler K, Antoons G, et al. Pharmacological modulation of connexin‐formed channels in cardiac pathophysiology[J]. British journal of pharmacology, 2011, 163(3): 469-483.
[2] Sathiyanadan K, Alonso F, Domingos-Pereira S, et al. Targeting endothelial Connexin37 reduces angiogenesis and decreases tumor growth[J]. International journal of molecular sciences, 2022, 23(6): 2930.
[3] Ribeiro-Rodrigues T M, Martins-Marques T, Morel S, et al. Role of connexin 43 in different forms of intercellular communication–gap junctions, extracellular vesicles and tunnelling nanotubes[J]. Journal of cell science, 2017, 130(21): 3619-3630.
[4] Maeda S, Tsukihara T. Structure of the gap junction channel and its implications for its biological functions[J]. Cellular and Molecular Life Sciences, 2011, 68(7): 1115-1129.
[5] Ilvesaro J, Tavi P, Tuukkanen J. Connexin-mimetic peptide Gap 27 decreases osteoclastic activity[J]. BMC musculoskeletal disorders, 2001, 2(1): 10.
[6] Elbadawy H M, Mirabelli P, Xeroudaki M, et al. Effect of connexin 43 inhibition by the mimetic peptide Gap27 on corneal wound healing, inflammation and neovascularization[J]. British journal of pharmacology, 2016, 173(19): 2880-2893.
[7] Lucero C M, Andrade D C, Toledo C, et al. Cardiac remodeling and arrhythmogenesis are ameliorated by administration of Cx43 mimetic peptide Gap27 in heart failure rats[J]. Scientific Reports, 2020, 10(1): 6878.
Gap 27是一种由连接蛋白43（Connexin43, Cx43）衍生而来的肽（Ser-Arg-Pro-Thr-Glu-Lys-Thr-Ile-Phe-Ile-Ile），是一种选择性间隙连接阻断剂[1, 2]。Gap 27通过模拟Cx43的一部分结构，特异性作用于该蛋白，从而抑制由Cx43介导的细胞间通讯[3]。间隙连接是相邻细胞膜上的通道结构，允许小分子物质在细胞间直接传递，对于协调细胞群体活动至关重要[4]。
在体外，Gap 27（500µM）处理培养在牛骨切片上的大鼠破骨细胞48h，显著降低了破骨细胞的存活率，减少了TRAP阳性单核和多核大鼠破骨细胞的数量[5]。Gap 27（0.1mM）处理原代人角膜上皮细胞（HCEC），增强了体外HCEC的伤口闭合[6]。
在体内，Gap 27（1µg/kg）通过渗透性微泵处理动静脉瘘模型（AV-Shunt）大鼠4周，显著减缓了大鼠心脏功能恶化的进展，显著改善了心脏功能[7]。