Synthesis of human ω-O-acylceramides and evaluation of their effects on barrier properties of skin lipid membranes

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic chemistry Candidate: Mgr. Lukáš Opálka Supervisor: doc. PharmDr. Kateřina Vávrová, Ph.D. Title of doctoral thesis: Synthesis of human ω-O-acylceramides and evaluation of their effects on barrier properties of skin lipid membranes The main objective of this work was to synthesize and study human acylceramides (acylCer, ceramides of the EO type) with the focus on the relationships between the acylCer concentration , structure of their polar head, their ability to form lamellar phases and permeability of model lipid membranes. Another objective was to synthesize ceramide-1-phosphates for the study of their signaling role in skin barrier and an analogue of ganglioside GM1 with shorter acyl chain as a standard for analysis of these lipids. Ceramides (Cer) belong to the family of sphingolipids. They are the central molecules in sphingolipid metabolism, they participate on cell regulatory processes and the formation of human skin lipid barrier. The main skin barrier is situated in the stratum corneum (SC), which is the uppermost layer of skin. The purpose of SC is to maintain homeostasis of the inner environment and to prevent the penetration of exogenous substances, allergens and bacteria to the..