The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity

Abstract

KTTKS is a matrikine that originates from the proteolytic hydrolysis of collagen. This peptide stimulates ECM production and types I and III collagen expression in vitro. A more stable form of KTTKS is pal-KTTKS, known as Matrixyl® or palmitoyl pentapeptide-3. A series of novel pentapeptides, analogues of KTTKS with the general formula X-KTTKS-OH(NH2), where X = acetyl, lipoyl, palmitoyl residues, was designed and synthesized. Their effect on amidolytic activity of urokinase, thrombin, trypsin, plasmin, t-PA, and kallikrein were tested. Cytotoxic tests on fibroblasts, as well as collagen and DNA biosynthesis tests for selected peptides, were also carried out. The test results showed that the most active plasmin inhibitors were palmitoyl peptides, whether in acid or amide form. No biological effects of lysine modification to arginine in the synthesized peptides were found. None of the synthesized peptides was not cytotoxic on fibroblasts, and three of them showed cell growth. These three compounds showed no concentration-activity relationship in the collagen and DNA biosynthesis assays.

Boosting Cosmeceutical Peptides: Coupling Imidazolium-Based Ionic Liquids to Pentapeptide-4 Originates New Leads with Antimicrobial and Collagenesis-Inducing Activities

“…The results shown in Table 5 , are expressed as the conjugate concentration causing a 50% cell growth inhibition (IC 50 ). As expected from previous reports ( 37 ), both the parent peptide sequence KTTKS and the derived reference cosmeceutical Matrixyl (C 16 -KTTKS- OH ) did not show relevant toxicity against the cell lines tested, at up to 100 μM. In turn, the parent IL [C 16 M1Im][Br] and its covalent equimolar mixture with PP4, KTTKS:[C 16 M1Im][Br] (1:1), were significantly toxic.…”

Optimized cutaneous delivery of anti-wrinkle dipeptide KT via molecular modification: Preformulation, permeation, and the importance of conjugate chain length

“…Fortunately, Pal-KT, which is a commercialized and stable form of KT, has partially overcome this obstacle. 17,18 However, it is a poorly water-soluble compound, and considering the molecular weight hindrance, as discussed above, it is expected to achieve more efficient lipoidal conjugates through using smaller and more hydrophilic moieties, the subject of the present investigation.…”

Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy

“…In vivo studies on 93 women, including placebo subjects, and conducted in a double-blind clinical study, show that an application of that palmitoylated peptide improves reduction of fine lines and wrinkles (Robinson et al, 2005). An advanced study on new analogs of Pentapetide-3 was recently published (Tałałaj et al, 2019).…”