The regulatory role of the tetrapeptide AcSDKP in skin and hair physiology and the prevention of ageing effects in these tissues – a potential cosmetic role

Abstract

The naturally occurring tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) recognized as a potent angiogenic factor was shown recently to contribute to the repair of cutaneous injuries. In the current article, we report the ability of AcSDKP to exert a beneficial effect on normal healthy skin and scalp and to compensate for the ageing process. In vitro AcSDKP at 10⁻¹¹-10⁻⁷ M significantly stimulates the growth of human keratinocytes, fibroblasts and follicle dermal papilla cells. Moreover, it enhances the growth of human epidermal keratinocyte progenitor and stem cells as shown in a clonogenic survival assay. Topical treatment of ex vivo cultured skin explants with 10⁻⁵ M AcSDKP increases the thickness of the epidermis and upregulates the synthesis of keratins 14 and 19, fibronectin, collagen III and IV as well as the glycoaminoglycans (GAGs). In the ex vivo-cultured hair follicles, AcSDKP promotes hair shaft elongation and induces morphological and molecular modifications matching the criteria of hair growth. Furthermore, AcSDKP at 10⁻¹¹-10⁻⁷ M was shown to improve epidermal barrier, stimulating expression of three protein components of tight junctions (claudin-1, occludin, ZO-1) playing an important role in connecting neighbouring cells. This tetrapeptide exercises also activation of SIRT1 implicated in the control of cell longevity. Indeed, a two-fold increase in the synthesis of SIRT1 by cultured keratinocytes was observed in the presence of 10⁻¹¹-10⁻⁷ M AcSDKP. In conclusion, these findings provide convincing evidence of the regulatory role of AcSDKP in skin and hair physiology and suggest a cosmetic use of this natural tetrapeptide to prevent skin ageing and hair loss and to promote the cutaneous regeneration and hair growth.

Review of Hair Follicle Dermal Papilla cells asin vitroscreening model for hair growth

“…Several peptide complexes, proteins and mimetics have also displayed significant hair growth potential in DPCs . Squarticles are the nanoparticles formed from sebum‐derived lipids such as squalene and fatty esters to achieve targeted drug delivery to the follicles.…”

Synthesis and bioactivity of a Goralatide analog with antileukemic activity

“…1 82 (m, 3H), 1.78-1.64 (m, 3H), 1.61-1.46 (m, 2H), 1.41 (s, 12H). 13 4.2.6. Benzyl N 6 -((benzyloxy)carbonyl)-L-lysyl-L-prolinate trifluoroacetate (10) TFA (15 mL) was added to a solution of benzyl N 0 -((benzyloxy)-carbonyl)-N-(tert-butoxycarbonyl)-L-lysyl-L-prolinate 9 in DCM (15 mL) at rt, and the mixture was stirred for 3 h. It was then concentrated in vacuum to give 10 (0.4 g, 85%) as yellow oil.…”

“…Benzyl N 6 -((benzyloxy)carbonyl)-L-lysyl-L-prolinate trifluoroacetate (10) TFA (15 mL) was added to a solution of benzyl N 0 -((benzyloxy)-carbonyl)-N-(tert-butoxycarbonyl)-L-lysyl-L-prolinate 9 in DCM (15 mL) at rt, and the mixture was stirred for 3 h. It was then concentrated in vacuum to give 10 (0.4 g, 85%) as yellow oil. 1 13 To a solution of benzyl N 2 -((S)-2-((S)-2-acetamido-3-(tert-butoxy)propanamido)-4-(tert-butoxy)-4-oxobutanoyl)-N 6 -(2-phenoxyacetyl)-L-lysyl-L-prolinate 11 (0.25 g, 0.5 mmol) in MeOH (10 mL) 10% Pd/C (0.03 g) was added and the resulting mixture was stirred under H 2 . When TLC showed no starting materials remained, the Pd/C was filtered on a pad of celite and the solution was then concentrated under reduced pressure to give a crude residue 12 which was dissolved in DCM (5 mL) followed the addition of TFA (5 mL) at 0°C.…”

“…7-10 New properties have recently been added to the Goralatide bioactivity profile that enhance the myelopoietic response to granulocyte-macrophage colony-stimulating factor (GM-CSF), 11 protect stem cells from hyperthermic damage, 12 and block doxorubicin-induced toxicity in vivo. 2 Goralatide also prevents skin and hair aging, 13 stimulates angiogenesis 14 and shows anti-inflammatory activity. 15,16 Despite a wide range of possible bioapplications, Goralatide 1a ( Fig.…”

Synthesis of L‐Lys‐Aminoxy‐Goralatide

“…It selectively protects the stem cell compartment during chemotherapy [5], enhances the myelopoietic response to granulocyte-macrophage colony-stimulating factor [6], selectively protects murine hematopoietic progenitors and stem cells from hyperthermic damage [6], and prevents doxorubicin-induced toxicity in mice [7]. Recently, AcSDKP 1 has been associated with (i) prevention of skin and hair aging [8], (ii) stimulation of angiogenesis [9] and (iii) antiinflammatory properties [10], and (iv) overexpression from thymosin β4 in neoplastic diseases [11].…”