AC-SER-ASP-LYS-PRO-OH

AcSDKP is an oligopeptide composed of acetyl-Ser-Asp-Lys-Pro. Found at low concentrations endogenously, AcSDKP is produced from thymosin and inhibits the phosphorylation of Smad2, therefore downsizing the expression of genes regulated by TGFβ. This mechanism mediates an antifibrotic effect and a reduction in edema. AcSDKP is catabolized almost exclusively by angiotensin converting enzyme I (ACEI), although ACEI-resistant analogs have been created. AcSDKP has been recognized as a potent inducer of angiogenesis and an anti-inflammatory agent, also contributing to its anti-fibrotic effects. Its cutaneous anti-aging effects have also been investigated. AcSDKP at a concentration of 10−7–10−11 stimulates the expression of proteins that strengthen tight junctions, including caludin-1, occluding, and ZO-1.
In an ex vivo study, topical AcSDKP accelerated skin healing after UV irradiation. AcSDKP also stimulates the proliferation of keratinocytes, fibroblasts, and epidermal basal layer cells. Topical application of 10−5 M AcSDKP also inhibits aging of human skin explants by significantly increasing epidermal thickness after only six days, increases collagen III along the papillary dermis and collagen IV along the basal membrane, with a concomitant increase in GAGs, especially HA. This peptide also modulates the growth of human hair in an ex vivo study. Treatment of normal human dermal fibroblast cells with AcSDKP showed increased collagen I synthesis and SIRTI, improving skin structure and increasing cell longevity.78 In one study, topically administered AcSDKP on an ex vivo skin-explant model significantly increases epidermis thickness after only six days of treatment with 10−8 M AcSKDP. In addition to upregulating the expression of collagen and fibronectin along the dermo-epithelial junction, AcSKDP also increases GAG deposited in the ECM, especially hyaluronic acid. Lastly, AcSDKP encourages dermal fibroblasts and keratinocytes to proliferate and modulates hair growth.

N-Acetyl-Ser-Asp-Lys-Pro inhibits the entry of pluripotent hemopoietic stem cells into S-phase of the cell cycle and protects against Ara-C lethality in mice. It is a specific substrate for the N-terminal active site of angiotensin converting enzyme, which is responsible for its degradation in vivo.