Effect of the six-mer synthetic peptide (AT1002) fragment of zonula occludens toxin on the intestinal absorption of cyclosporin A

Intestinal permeation enhancers for oral peptide delivery

“…This short peptide sequence was designated AT1002 (H-FCIGRL-OH) (Alba Therapeutics (USA)) [111]. While the enhancement action of AT1002 was reversible, high mg concentrations were required to induce a 40-fold enhancement of Lucifer Yellow in Caco-2 monolayers [111] and in addition, the peptide did not increase duodenal absorption of cyclosporin A unless co-administered with a peptidase inhibitor (bestatin) and a surfactant (benzalkonium chloride) [115]. Melittin is a small cell penetrating-and antimicrobial peptide that also modulates the function of a number of mammalian receptors and signalling proteins (e.g.…”

Development of an Efficient Transdermal Delivery System of Small Interfering RNA Using Functional Peptides, Tat and AT-1002

“…As an alternative to Zot, advances in the study of structure-activity relationships have led to the identification of AT1002, a novel tight junction modulator peptide. 16,17) AT1002 is a six-mer synthetic peptide that retains non-toxic biological activity by reversibly opening tight junctions, like Zot, and increases paracellular transport of drugs across the epithelial barrier.…”

Recent progress in tight junction modulation for improving bioavailability

“…In contrast to many unspecific TJ modulators, it has the ability to reversibly increase the paracellular permeability in a dose-dependent, non-cytotoxic manner by specific activation of the protease activated receptor-2 (PAR-2) (zonulin) receptor involved in TJ regulation [61,68,69]. AT1002 was derived from the ZO toxin (Zot) through a detailed analysis of structure--activity relationships that revealed that this short peptide sequence constitutes the minimum structural requirements for biological activity [68].…”

“…Stabilization in solutions of pH 7.4 (up to 6 h) is obtained with 5% dextrose [84]. Similar to delta G [78,80], AT1002 needs to be combined with protease inhibitors for oral administration to protect against gastrointestinal peptide degradation [69].…”