A peptidomimetic with a chiral switch is an inhibitor of epidermal growth factor receptor heterodimerization.

Among different types of EGFR dimers, EGFR-HER2 and HER2-HER3 are well known in different types of cancers. Targeting dimerization of EGFR will have a significant impact on cancer therapies. A symmetric peptidomimetic was designed to inhibit the protein-protein interaction of EGFR.

Engineered Theranostic Magnetic Nanostructures: Role of Composition and Surface Coating on Magnetic Resonance Imaging Contrast and Thermal Activation.

Magnetic nanostructures (MNS) have emerged as promising functional probes for simultaneous diagnostics and therapeutics (theranostic) applications due to their ability to enhance localized contrast in magnetic resonance imaging (MRI) and heat under external radio frequency (RF) field, respectively. We show that the "theranostic" potential of the MNS can be significantly enhanced by tuning their core composition and architecture of surface coating. Metal ferrite (e.

Expression and purification of HER2 extracellular domain proteins in Schneider2 insect cells.

Overexpression of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu) results in ligand independent activation of kinase signaling and is found in about 30% of human breast cancers, and is correlated with a more aggressive tumor phenotype. The HER2 extracellular domain (ECD) consists of four domains - I, II, III and IV. Although the role of each domain in the dimerization and activation of the receptor has been extensively studied, the role of domain IV (DIV) is not clearly understood yet.

Current and future targeted therapies for non-small-cell lung cancers with aberrant EGF receptors.

Expression of the EGF receptors (EGFRs) is abnormally high in many types of cancer, including 25% of lung cancers. Successful treatments target mutations in the EGFR tyrosine kinase domain with EGFR tyrosine kinase inhibitors (TKIs). However, almost all patients develop resistance to this treatment, and acquired resistance to first-generation TKI has prompted the clinical development of a second generation of EGFR TKI.

Novel Peptidomimetics for Inhibition of HER2:HER3 Heterodimerization in HER2-Positive Breast Cancer.

The current approach to treating HER2-overexpressed breast cancer is the use of monoclonal antibodies or a combination of antibodies with traditional chemotherapeutic agents or kinase inhibitors. Our approach is to target clinically validated HER2 domain IV with peptidomimetics and inhibit the protein-protein interactions (PPI) of HERs. Unlike antibodies, peptidomimetics have advantages in terms of stability, modification, and molecular size.

Structure-activity relationships of peptidomimetics that inhibit PPI of HER2-HER3.

Human epidermal growth factor receptor-2 (HER2) is a tyrosine kinase family protein receptor that is known to undergo heterodimerization with other members of the family of epidermal growth factor receptors (EGFR) for cell signaling. Overexpression of HER2 and deregulation of signaling has implications in breast, ovarian, and lung cancers. We have designed several peptidomimetics to block the HER2-mediated dimerization, resulting in antiproliferative activity for cancer cells.

Immunosuppression by co-stimulatory molecules: inhibition of CD2-CD48/CD58 interaction by peptides from CD2 to suppress progression of collagen-induced arthritis in mice.

Targeting co-stimulatory molecules to modulate the immune response has been shown to have useful therapeutic effects for autoimmune diseases. Among the co-stimulatory molecules, CD2 and CD58 are very important in the early stages of generation of an immune response. Our goal was to utilize CD2-derived peptides to modulate protein-protein interactions between CD2 and CD58, thereby modulating the immune response.

Stability and in vitro antiproliferative activity of bioactive "Vitamin E" fortified parenteral lipid emulsions.

The objectives of this work were to engineer physically stable "Vitamin E" rich intravenous lipid emulsions and to evaluate their in vitro antiproliferative activity against MCF-7 (human mammary adenocarcinoma) and SW-620 (human colon adenocarcinoma) cell lines. Emulsions loaded with 70% vitamin E by total weight of the oil phase were stabilized with secondary emulsifiers and tested for their hemolytic effect and their plasma and electrolyte stability. Emulsions stabilized with sodium oleate and sodium deoxycholate were sensitive to electrolytes and exhibited significant hemolytic effect.