Lipoxygenases at the Intersection of Infection and Carcinogenesis.

The persisting presence of opportunistic pathogens like Pseudomonas aeruginosa poses a significant threat to many immunocompromised cancer patients with pulmonary infections. This review highlights the complexity of interactions in the host's defensive eicosanoid signaling network and its hijacking by pathogenic bacteria to their own advantage. Human lipoxygenases (ALOXs) and their mouse counterparts are integral elements of the innate immune system, mostly operating in the pro-inflammatory mode. Taking into account the indispensable role of inflammation in carcinogenesis, lipoxygenases have counteracting roles in this process. In addition to describing the structure-function of lipoxygenases in this review, we discuss their roles in such critical processes as cancer cell signaling, metastases, death of cancer and immune cells through ferroptosis, as well as the roles of ALOXs in carcinogenesis promoted by pathogenic infections. Finally, we discuss perspectives of novel oncotherapeutic approaches to harness lipoxygenase signaling in tumors.

Reactive trityl derivatives: stabilised carbocation mass-tags for life sciences applications.

The rational design of novel triarylmethyl (trityl)-based mass tags (MT) for mass-spectrometric (MS) applications is described. We propose a "pK(R+) rule" to correlate the stability of trityl carbocations with their MS performance: trityls with higher pK(R+) values ionise and desorb better. Trityl blocks were synthesised that have high pK(R+) values and are stable in conditions of MS analysis; these MTs can be ionised by matrix as well as irradiation with a 337 nm nitrogen laser. (13)C-Labelled tags were prepared for MS quantitation applications. Moreover, the tags were equipped with a variety of functional groups allowing conjugation with different functionalities within (bio)molecules to enhance the MS characteristics of the latter. The MS behaviour of model polycationic trityl compounds with and without the matrix was studied to reveal that poly-trityl clusters are always singly charged under the (MA)LDI-TOF conditions. Several peptide-trityl conjugates were prepared and comparisons revealed a beneficial effect of trityl tags on the conjugate detection in MS. Trityl compounds containing para-methoxy- and dimethylamine groups, as well as a xanthene fragment, showed considerable enhancement in MS detection of model peptides; thus they are promising tools for proteomic applications. Dimethoxytrityl derivatives allow one to distinguish between Arg- and Lys-containing peptides. Maleimido trityl derivatives are suitable for the efficient derivatisation of thiol-containing peptides in pyridine.