CALP1 (trifluoroacetate salt) is an eight-residue complementary peptide that binds to the calcium-binding sites (the EF hand) of calmodulin [1]. CALP1 (trifluoroacetate salt) interacts with the two carboxyl-terminal Ca2+-binding sites of calmodulin as well as the EF hands of troponin C, which results in a conformational change and activates phosphodiesterase in the absence of Ca2+[2]. CALP1 (trifluoroacetate salt) has been widely used in allergic asthma models to mitigate the development of airway hyperresponsiveness [3].
In vitro, CALP1 (trifluoroacetate salt) treatment (20µM) for 2 hours can increase the expression of the VPAC1 protein on the surface of monocytes infected by Salmonella[4]. 100µM of CALP1 (trifluoroacetate salt) pretreatment for 15 minutes can reduce the excessive cytoplasmic Ca2+ signal and necrosis in mouse pancreatic acinar cells (PACs) induced by BH3I-2′[5]. Treatment with 100µM CALP1 (trifluoroacetate salt) for 60 minutes can inhibit the adhesion of murine bone marrow-derived mast cells (BMMCs) to fibronectin induced by FcεRI[6]. Treatment with 10µM CALP1 (trifluoroacetate salt) for 48 hours significantly inhibited the expression of TGF-β2 and IL-10 in C2C12 cells and promoted the upregulation of p-CaMKII, p-CaMKIV, and NFATc2 levels after IFN-γ stimulation[7].
In vivo, thirty minutes before ovalbumin challenge, a single dose of CALP1 (trifluoroacetate salt) (1mg/ml; 0.1ml) was injected intratracheally, significantly reducing the infiltration of alveolar macrophages in the lungs of guinea pigs stimulated by ovalbumin and inhibiting the generation of free radicals[8].
References:
[1] Folkerts G, Nijkamp F P. Airway nitrergic pathways: is there therapeutic potential in asthma and COPD?[J]. Current Opinion in Pharmacology, 2004, 4(3): 202-206.
[2] Villain M, Jackson P L, Manion M K, et al. De novo design of peptides targeted to the EF hands of calmodulin[J]. Journal of Biological Chemistry, 2000, 275(4): 2676-2685.
[3] Ten Broeke R, Leusink-Muis T, Hilberdink R, et al. Specific modulation of calmodulin activity induces a dramatic production of superoxide by alveolar macrophages[J]. Laboratory investigation, 2004, 84(1): 29-40.
[4] Askar B, Higgins J, Barrow P, et al. Immune evasion by Salmonella: exploiting the VPAC 1/VIP axis in human monocytes[J]. Immunology, 2019, 158(3): 230-239.
[5] Ferdek P E, Jakubowska M A, Nicolaou P, et al. BH3 mimetic-elicited Ca2+ signals in pancreatic acinar cells are dependent on Bax and can be reduced by Ca2+-like peptides[J]. Cell Death & Disease, 2017, 8(3): e2640-e2640.
[6] Houtman R, Ten Broeke R, Blalock J E, et al. Attenuation of very late antigen-5-mediated adhesion of bone marrow-derived mast cells to fibronectin by peptides with inverted hydropathy to EF-hands[J]. The Journal of Immunology, 2001, 166(2): 861-867.
[7] Hu J, Shi D, Ding M, et al. Calmodulin‐dependent signalling pathways are activated and mediate the acute inflammatory response of injured skeletal muscle[J]. The Journal of physiology, 2019, 597(21): 5161-5177.
[8] Ten Broeke R, Brandhorst M C, Leusink-Muis T, et al. Ca2+ sensors modulate asthmatic symptoms in an allergic model for asthma[J]. European journal of pharmacology, 2003, 476(1-2): 151-157.
CALP1 (trifluoroacetate salt)是一种由八个残基组成的互补肽，可结合钙调蛋白的钙结合位点（EF手结构域）[1]。CALP1 (trifluoroacetate salt)与钙调蛋白的两个羧基末端Ca2+结合位点以及肌钙蛋白C的EF手形结构相互作用，导致构象变化，并在无Ca2+条件下激活磷酸二酯酶[2]。CALP1 (trifluoroacetate salt)已被广泛用于过敏性哮喘模型，以减轻气道高反应性的发展[3]。
在体外，20µM的CALP1 (trifluoroacetate salt)处理2小时可增加感染沙门氏菌的单核细胞表面VPAC1蛋白的表达[4]。100µM的CALP1 (trifluoroacetate salt)预处理15分钟可减少BH3I-2′诱导的小鼠胰腺腺泡细胞(PACs)中过度的细胞质Ca2+信号和坏死[5]。100µM的CALP1 (trifluoroacetate salt)处理60分钟可抑制FcεRI诱导的小鼠骨髓来源肥大细胞(BMMCs)与纤连蛋白的粘附[6]。10µM的CALP1 (trifluoroacetate salt)处理C2C12细胞48小时，显著抑制了TGF-β2和IL-10的表达，并在IFN-γ刺激后促进 p-CaMKII、p-CaMKIV和NFATc2水平的上调[7]。
在体内，在卵清蛋白激发前30分钟，单次气管内注射（0.1ml）1mg/ml的CALP1 (trifluoroacetate salt)，可显著减少卵清蛋白刺激的豚鼠肺部肺泡巨噬细胞的浸润，并抑制自由基的产生[8]。