ABSTRACT
The 'matrikine' concept claims that processing of the precursors for collagen results in the formation of peptides such as KTTKS which in turn augments extracellular matrix (ECM) production. In the present study, we show the development of an anti-ageing active from an in silico approach by molecular design resulting in the tetrapeptide GEKG derived from ECM proteins. The efficacy of the peptide to significantly induce collagen production of the protein level and mRNA level has been demonstrated in vitro in human dermal fibroblasts and in vivo in a double-blind, randomized, placebo-controlled study enroling 10 volunteers with an average age of 48.2 years. The effect of GEKG on facial wrinkles was studied in 30 volunteers using state of the art fringe projection, which allows determination of surface roughness in three-dimensions. Here, only GEKG but not the placebo was able to significantly decrease skin roughness as a measure for wrinkles.
Subject(s)
Extracellular Matrix/metabolism , Oligopeptides/pharmacology , Skin Aging/drug effects , Adult , Cells, Cultured , Collagen Type I/genetics , Collagen Type I/metabolism , Collagen Type I, alpha 1 Chain , Dermatologic Agents/pharmacology , Dermatologic Agents/therapeutic use , Double-Blind Method , Elasticity/drug effects , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibronectins/genetics , Fibronectins/metabolism , Gene Expression/genetics , Glucuronosyltransferase/genetics , Humans , Hyaluronan Synthases , Hyaluronic Acid/metabolism , Oligopeptides/therapeutic use , Procollagen/metabolism , Skin/drug effects , Skin/metabolism , Skin Physiological Phenomena/drug effectsABSTRACT
Laspartomycin was originally isolated and characterized in 1968 as a lipopeptide antibiotic related to amphomycin. The molecular weight and structure remained unknown until now. In the present study, laspartomycin was purified by a novel calcium chelate procedure, and the structure of the major component (1) was determined. The structure of laspartomycin C (1) differs from that of amphomycin and all related antibiotics as a result of its peptide region being acidic rather than amphoteric and the amino acid branching into the side chain being diaminopropionic rather than diaminobutyric. In addition, the fatty acid side chain is 2,3-unsaturated compared to 3,4-unsaturated for amphomycin and other related antibiotics. Calcium ion addition to stabilize a particular conformer was found to be important for an enzymatic deacylation of the antibiotic. A peptide resulting from the deacylation was critical for chemical structure determination by NMR studies, which also involved addition of calcium ions to stabilize a conformer.
