Susan Jane Tzotzos

Freelance

Tumor necrosis factor (TNF) is a homotrimer that has two spatially distinct binding regions, three lectin-like domains (LLD) at the TIP of the protein and three basolaterally located receptor-binding sites, the latter of which are responsible for the inflammatory and cell death-inducing properties of the cytokine. Solnatide (a.k.a. TIP peptide, AP3...

Stapled peptides are synthetic peptidomimetics of bioactive sites in folded proteins, which carry chemical links, introduced during peptide synthesis, designed to retain the secondary structure in the native protein molecule. Stapled peptides have been investigated as potential modulators of protein‐protein interactions for over two decades. The po...

Previous in vitro studies have indicated that tumor necrosis factor (TNF) activates amiloride-sensitive epithelial sodium channel (ENaC) current through its lectin-like (TIP) domain, since cyclic peptides mimicking the TIP domain (e.g., solnatide), showed ENaC-activating properties. In the current study, the effects of TNF and solnatide on individu...

The synthetically produced cyclic peptides solnatide (a.k.a. TIP or AP301) and its congener AP318, whose molecular structures mimic the lectin-like domain of human tumor necrosis factor (TNF), have been shown to activate the epithelial sodium channel (ENaC) in various cell- and animal-based studies. Loss-of-ENaC-function leads to a rare, life-threa...

Regulation of the epithelial sodium channel (ENaC), which regulates fluid homeostasis and blood pressure, is complex and remains incompletely understood. The TIP peptide, a mimic of the lectin-like domain of TNF, activates ENaC by binding to glycosylated residues in the extracellular loop of ENaC-α as well as to a hitherto uncharacterized internal...

AP301 is an activator of ENaC-mediated Na(+) uptake for the treatment of pulmonary permeability edema in acute respiratory distress syndrome (ARDS). The purpose of this "first-in-man" study was to examine local and systemic safety and systemic exposure of ascending single doses of AP301, when inhaled by healthy male subjects. In a double-blind, pla...

AP301, a cyclic peptide, comprising the human tumour necrosis factor lectin like domain (TIP domain) sequence, is currently being developed as a therapy for lung oedema and has been shown to reduce extravascular lung water and improve lung function in a mouse, rat and pig model. The current paradigm for liquid homeostasis in the adult mammalian lun...

Rationale: Aims of this study were to investigate whether the TIP peptide, mimicking the alveolar liquid clearance (ALC)-promoting lectin-like domain of TNF, is able to activate amiloride-sensitive Na+ transport in H441 cells and to directly interact with specific ENaC domains. Methods: Peptide effects on Na+-uptake in cells pretreated or not with...

Pulmonary edema is a major complication of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) which is associated with higher mortality. AP301 is a synthetic peptide whose structure is based on the lectin-like domain of human Tumour Necrosis Factor alpha. The water soluble peptide can be administered into the lung by oral inhala...

The amiloride-sensitive epithelial sodium channel (ENaC) plays a prominent role in sodium uptake from alveolar fluid and is the major component in alveolar fluid clearance in normal and diseased lungs. The lectin-like domain of TNF-α has been shown to activate amiloride-sensitive sodium uptake in type II alveolar epithelial cells. Therefore, severa...

Numerous short peptides have been shown to form beta-sheet amyloid aggregates in vitro. Proteins that contain such sequences are likely to be problematic for a cell, due to their potential to aggregate into toxic structures. We investigated the structures of 30 proteins containing 45 sequences known to form amyloid, to see how the proteins cope wit...

Numerous short peptides have been shown to form b-sheet amyloid aggregates in vitro. Proteins that contain such sequences are likely to be problematic for a cell, due to their potential to aggregate into toxic structures. We investigated the structures of 30 proteins containing 45 sequences known to form amyloid, to see how the proteins cope with t...

OBJECTIVE: To study and evaluate changes in the gyrA gene and the outer-membrane protein patterns in relation to evolution of resistance against the quinolones in Enterobacter cloacae. METHODS: Strains expressing gyrA-mediated quinolone resistance become susceptible to quinolones upon insertion of the plasmid pNJR3-2. This plasmid (containing wild-...

Clinical assessment, haematological studies, and globin gene mapping were performed in 21 Greek subjects with haemoglobin H disease. Clinical phenotypes ranged from mild, and virtually asymptomatic, to severe cases requiring transfusion. The severe clinical phenotype was exclusively associated with non-deletion genotypes, whereas the mild and inter...

The prevalence and molecular basis of α-thalassemia in Greece was studied. To estimate the prevalence of α-thalassemia, 227 cord blood samples were examined by haematological and gene mapping techniques. Amongst the 227 newborns, 16(7.05%) α-thalassemia 2(-α3-7/αα) and 2(0.88%) α-thalassemia 1 (--Med/αα and -(α)20.5;αα) heterozygotes were found. On...

Using hematological and gene mapping techniques, a cord blood survey was carried out to estimate the frequency of alpha-thalassemia in the Greek population. Out of 227 newborns studied, 16 (7.05%) were found by gene mapping to be alpha-thalassemia 2 heterozygotes (-alpha/alpha alpha), and of these only two had increased levels of hemoglobin Bart's...

Globin gene mapping in 16 Greek individuals with HbH disease and their parents has demonstrated the occurrence of several HbH genotypes brought about by the interaction of two alpha zero-thalassaemia and two alpha+-thalassaemia haplotypes. Eight of the 16 patients had the genotype - -Med/-alpha 3.7, four the genotype -(alpha)20.5/-alpha 3.7 and thr...