The formation of local secondary structure is an essential step in the folding of a polypeptide from a random coil to a well-defined native conformation. Detection of hidden structural propensities in amino acid sequences may provide important insight into how this is accomplished. 2,2,2-Trifluoroethanol (TFE) has been shown to induce helical structure in polypeptides, and TFE titration has been used as a qualitative probe for helical tendency. We have investigated the propensity of five synthetic peptides to adopt helical structure in TFE. The free energy of helix formation exhibits linear dependence on the mole ratio of TFE to water, and the constant of proportionality (m-value) can be perturbed systematically by altering the peptide length and unsystematically by altering the temperature. Three peptides with closely related sequences but different N-cap residues show different titration behavior from 5 to 75 degrees C, suggesting that TFE acts only within the context of a preexisting helix-coil equilibrium. These observations can be reconciled with a model for TFE/H2O exchange at peptide binding sites. Our results support the viability of TFE titration as a tool for extrapolation of quantitative helix-coil equilibrium constants for peptides with little or no apparent helical content in aqueous solution.
Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gdfree contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterioncoated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T 1 contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography. exceedingly small iron oxide nanoparticles | renal clearance | gadoliniumfree positive MR contrast agent | preclinical magnetic resonance imaging M RI signal arises from the excitation of low-energy nuclear spins, which are formed in a permanent magnetic field, by applying radiofrequency pulses followed by the measurement of the spin relaxation processes (i.e
Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magnetofluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close-packed magnetic nanoparticle 'core', which is fully surrounded by a 'shell' of fluorescent quantum dots. A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality. We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.
Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field 1H MRI techniques.
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