The transfer free energies of the twenty natural amino acid side chains from water to phospholipid bilayers make a major contribution to the assembly and function of membrane proteins. Measurements of those transfer free energies will facilitate the identification of membrane protein sequences and aid in the understanding of how proteins interact with membranes during key biological events. We report the first water-to-bilayer transfer free energy scale (i.e., a “hydrophobicity scale”) for the twenty natural amino acid side chains measured in the context of a native transmembrane protein and a phospholipid bilayer. Our measurements reveal parity for apolar side-chain contributions between soluble and membrane proteins and further demonstrate that an arginine side-chain placed near the middle of a lipid bilayer is accommodated with much less energetic cost than predicted by molecular dynamics simulations.

https://www.pnas.org/content/pnas/108/25/10174.full.pdf

Side-chain hydrophobicity scale derived from transmembrane protein folding into lipid bilayers

Vibrational spectroscopy provides a direct route to the physicochemical characterization of molecules. While both IR and Raman spectroscopy have been used for decades to provide detailed characterizations of small molecules, similar studies with proteins are largely precluded due to spectral congestion. However, the vibrational spectra of proteins do include a “transparent window”, between ∼1800 and ∼2500 cm–1, and progress is now being made to develop site-specifically incorporated carbon–deuterium (C–D), cyano (CN), thiocyanate (SCN), and azide (N3) “transparent window vibrational probes” that absorb within this window and report on their environment to facilitate the characterization of proteins with small molecule-like detail. This Review opens with a brief discussion of the advantages and limitations of conventional vibrational spectroscopy and then discusses the strengths and weaknesses of the different transparent window vibrational probes, methods by which they may be site-specifically incorporate...

Transparent Window Vibrational Probes for the Characterization of Proteins With High Structural and Temporal Resolution.

Ovarian carcinoma (OC) is the fifth leading cause of death among women in the United States. Persistent activation of signal transducer and activator of transcription (STAT3) is frequently detected in OC. STAT3 is activated by Janus family kinases (JAK) via cytokine receptors, growth factor receptor and non-growth factor receptor tyrosine kinases. Activation of STAT3 mediates tumor cell proliferation, survival, motility, invasion, and angiogenesis, and recent work demonstrates that STAT3 activation suppresses anti-tumor immune responses and supports tumor-promoting inflammation. We hypothesized that therapeutic targeting of the JAK/STAT3 pathway would inhibit tumor growth by direct effects on OC cells and by inhibition of cells in the tumor microenvironment (TME). To test this, we evaluated the effects of a small molecule JAK inhibitor, AZD1480, on cell viability, apoptosis, proliferation, migration and adhesion of OC cells in vitro. We then evaluated the effects of AZD1480 on in vivo tumor growth and progression, gene expression, tumor-associated matrix metalloproteinase (MMP) activity and immune cell populations in a transgenic mouse model of OC. AZD1480-treatment inhibited STAT3 phosphorylation and DNA binding, and migration and adhesion of cultured OC cells and ovarian tumor growth rate, volume and ascites production in mice. In addition, drug treatment led to altered gene expression, decreased tumor-associated MMP activity, and fewer suppressor T cells in the peritoneal tumor microenvironment of tumor-bearing mice than control mice. Taken together, our results show pharmacological inhibition of the JAK2/STAT3 pathway leads to disruption of functions essential for ovarian tumor growth and progression and represents a promising therapeutic strategy.

https://mct.aacrjournals.org/content/molcanther/14/4/1035.full.pdf

Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth

Effect of Polysorbate 20 and Polysorbate 80 on the Higher-Order Structure of a Monoclonal Antibody and Its Fab and Fc Fragments Probed Using 2D Nuclear Magnetic Resonance Spectroscopy

Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH (pHe), increased interstitial fluid pressure, altered choline phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprogramming, beyond aerobic glycolysis, in the course of tumor development and progression. The resulting altered metabolic content in tumors has the ability to affect cell signaling and block cellular differentiation. Additional emerging evidence reveals that the interaction between tumor and stroma cells can alter tumor metabolism (leading to metabolic reprogramming) as well as tumor growth and vascular features. This review will summarize previous and current preclinical, non-invasive, multimodal imaging efforts to characterize the tumor microenvironment, including its stromal components, and understand tumor-stroma interaction in cancer development, progression and treatment response.

/pdf/characterization-of-the-tumor-microenvironment-and-tumor-4bt4i6n00u.pdf

Characterization of the Tumor Microenvironment and Tumor–Stroma Interaction by Non-invasive Preclinical Imaging

Structural characterization of an equilibrium unfolding intermediate in cytochrome c.

Combined in vivo molecular and anatomic imaging for detection of ovarian carcinoma-associated protease activity and integrin expression in mice.

Introduction
Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging.

/pdf/mmp-13-in-vivo-molecular-imaging-reveals-early-expression-in-1u4secx0tm.pdf

MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma.

An imaging cassette. The cassette includes a top frame, a bottom frame, and one or more of a front wall, back wall, or plurality of posts, and defines a chamber for holding an animal in a desired position for analysis in a fluorescence molecular tomography imager and a vertical bore magnetic resonance imager.

Navid A. Roder

Papers

Structural characterization of an equilibrium unfolding intermediate in cytochrome c.

Combined in vivo molecular and anatomic imaging for detection of ovarian carcinoma-associated protease activity and integrin expression in mice.

MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma.

Systems for fusion of fluorescence molecular tomography and magnetic resonance images