AT-1002 TFA is a six-mer synthetic peptide that decreases transepithelial electrical resistance (TEER)[1]. AT-1002 TFA changes the structure of actin and ZO-1 proteins in epithelial cells, dissolving the tight junction[2]. AT-1002 TFA is widely used as the delivery enhancer for accelerating transdermal siRNA delivery in mouse models[3]. AT-1002 TFA can be used to prepare a novel protein coronal cationic liposome to improve the intestinal internalization of oral drugs and prolong the intestinal absorption time[4].
In vitro, AT-1002 TFA treatment at 7mM for 3h caused redistribution of ZO-1 and rearrangement of actin in Caco-2 BBE cells [5].
In vivo, AT-1002 TFA (300μg in 200μl of normal saline) combined with salmon calcitonin (sCT) (10μg in 200μl of normal saline) administered (intratracheal instillation) for one hour resulted in increased sCT absorption in rat lungs[6].
References:
[1] Li M, Oliver E, Kitchens K M, et al. Structure–activity relationship studies of permeability modulating peptide AT-1002[J]. Bioorganic & medicinal chemistry letters, 2008, 18(16): 4584-4586.
[2] Khaleghi S, Ju J M, Lamba A, et al. The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate[J]. Therapeutic advances in gastroenterology, 2016, 9(1): 37-49.
[3] Uchida T, Kanazawa T, Takashima Y, et al. Development of an efficient transdermal delivery system of small interfering RNA using functional peptides, Tat and AT-1002[J]. Chemical and Pharmaceutical Bulletin, 2011, 59(2): 196-201.
[4] Ding R, Zhao Z, He J, et al. Preparation, drug distribution, and in vivo evaluation of the safety of protein corona liposomes for liraglutide delivery[J]. Nanomaterials, 2023, 13(3): 540.
[5] Gopalakrishnan S, Durai M, Kitchens K, et al. Larazotide acetate regulates epithelial tight junctions in vitro and in vivo[J]. Peptides, 2012, 35(1): 86-94.
[6] Gopalakrishnan S, Pandey N, Tamiz A P, et al. Mechanism of action of ZOT-derived peptide AT-1002, a tight junction regulator and absorption enhancer[J]. International journal of pharmaceutics, 2009, 365(1-2): 121-130.
AT-1002 TFA 是一种六聚体合成肽，可降低跨上皮细胞电阻（TEER）[1]。AT-1002 TFA能改变上皮细胞中肌动蛋白和ZO-1蛋白的结构，从而溶解紧密连接[2]。AT-1002 TFA被广泛用作递送增强剂，以加速小鼠模型中的透皮siRNA递送[3]。AT-1002 TFA可用于制备一种新型蛋白冠状阳离子脂质体，以改善口服药物的肠道内化并延长肠道吸收时间[4]。
在体外，用7mM的AT-1002 TFA处理Caco-2 BBE细胞3小时，会导致ZO-1重新分布和肌动蛋白重排[5]。
在体内，将AT-1002 TFA（300μg溶于200μl生理盐水）与鲑鱼降钙素（sCT）（10μg溶于200μl生理盐水）联合通过气管内滴注给药一小时，增加了大鼠肺部对sCT的吸收[6]。