Lipidation of Naturally Occurring α-Helical Antimicrobial Peptides as a Promising Strategy for Drug Design.

In this paper, we describe the chemical synthesis, preliminary evaluation of antimicrobial properties and mechanisms of action of a novel group of lipidated derivatives of three naturally occurring α-helical antimicrobial peptides, LL-I (VNWKKVLGKIIKVAK-NH2), LK6 (IKKILSKILLKKL-NH2), ATRA-1 (KRFKKFFKKLK-NH2). The obtained results showed that biological properties of the final compounds were defined both by the length of the fatty acid and by the structural and physico-chemical properties of the initial peptide. We consider C8-C12 length of the hydrocarbon chain as the optimal for antimicrobial activity improvement. However, the most active analogues exerted relatively high cytotoxicity toward keratinocytes, with the exception of the ATRA-1 derivatives, which had a higher selectivity for microbial cells. The ATRA-1 derivatives had relatively low cytotoxicity against healthy human keratinocytes but high cytotoxicity against human breast cancer cells. Taking into account that ATRA-1 analogues carry the highest positive net charge, it can be assumed that this feature contributes to cell selectivity. As expected, the studied lipopeptides showed a strong tendency to self-assembly into fibrils and/or elongated and spherical micelles, with the least cytotoxic ATRA-1 derivatives forming apparently smaller assemblies. The results of the study also confirmed that the bacterial cell membrane is the target for the studied compounds.

[The role of proprotein convertases in cancer diseases with particular focus on PACE4]. / Rola konwertaz probialkowych w chorobach nowotworowych ze szczególnym uwzglednieniem enzymu PACE4.

Cancer is one of the most common cause of death nowadays. Thorough knowledge of the mechanisms of tumorigenesis and invasiveness of tumor cells is crucial for the development of molecular targeted therapies, which are believed to be future treatment of this type of diseases. Proteolytic enzymes are one of the factors involved in the development of cancer cells, very often used as markers of tumor progression. In this paper we describe the role of enzymes termed proprotein convertases (PCs) in pathogenesis and progress of cancer diseases. Furthermore, we indicate potential directions for the development of therapeutic strategies designed based on PCs inhibitors.

What can public endorsement for a smoking ban policy mean? Preliminary findings from a qualitative study.

OBJECTIVES: The aim of the study is to describe attitudes which underlie Pole's declarations of support for a smoking ban in public places. METHODS: The qualitative study using semi-structured individual in-depth interviews was conducted. The 30 IDI-s (in depth interviews) being a part of a larger research project entitled 'Lay meanings of health and life orientation of Polish society versus prevention and health promotion attitudes' were realized between 2007-2009. People belonging to all key socio-demographic categories identified by variables such as sex, age, education, and place of domicile were interviewed. The resulting material was subjected to content analysis. In the study the structural concept of 'attitude' was adopted. In order to identify the attitudes towards smoking bans in public places statements related to all three components of attitudes were analysed, but the typology of attitudes was constructed mainly on the basis of the emotional-evaluative component. RESULTS: The study identified as many as four attitudes behind the declared support for a smoking ban in public places. Those attitudes were labelled 'supportive', 'accepting', 'conditionally accepting', and 'ambivalent'. They differ as regards degree of acceptance for the ban, conviction about harmfulness of passive smoking, setting great store by other regulators of smoking like cultural norms or healthy consciousness, and propensity to observe and execute the smoking ban. The 'supportive' attitude can be characterized not only by total support for the smoking ban in public places but also by insistence on the need for its extension. The 'accepting' attitude means approval for the smoking ban, and the 'conditionally accepting' attitude is distinguished from the others by the stress put on the right of smokers to have an access to places where smoking is permitted. The 'ambivalent' attitude can be typified by underlining other than legal ways of influencing smoking in public places. CONCLUSIONS: The study suggests that the attitudes underlying the Pole's declarations of support for a smoking ban in public places can be differentiated. However, because of the low number of participants in the study the results should be verified thus the further research is needed. Therefore, there is a need not only to study people's declaration of support or objection for the smoking ban in public places but also to examine their attitudes including cognitive and behavioural components using both qualitative and quantitative methods of social research.