Site-selective protein modification via disulfide rebridging for fast tetrazine/trans-cyclooctene bioconjugation

An inverse electron demand Diels–Alder reaction between tetrazine and trans-cyclooctene (TCO) holds great promise for protein modification and manipulation. Herein, we report the design and synthesis of a tetrazine-based disulfide rebridging reagent, which allows the site-selective installation of a tetrazine group into disulfide-containing peptides and proteins such as the hormone somatostatin (SST) and the antigen binding fragment (Fab) of human immunoglobulin G (IgG). The fast and efficient conjugation of the tetrazine modified proteins with three different TCO-containing substrates to form a set of bioconjugates in a site-selective manner was successfully demonstrated for the first time. Homogeneous, well-defined bioconjugates were obtained underlining the great potential of our method for fast bioconjugation in emerging protein therapeutics. The formed bioconjugates were stable against glutathione and in serum, and they maintained their secondary structure. With this work, we broaden the scope of tetrazine chemistry for site-selective protein modification to prepare well-defined SST and Fab conjugates with preserved structures and good stability under biologically relevant conditions

Spectral properties and magneto-optical excitations in semiconductor double-rings under Rashba spin-orbit interaction

We have numerically solved the Hamiltonian of an electron in a semiconductor double ring subjected to the magnetic flux and Rashba spin-orbit interaction. It is found that the Aharonov-Bohm energy spectrum reveals multi-zigzag periodic structures. The investigations of spin-dependent electron dynamics via Rabi oscillations in two-level and three-level systems demonstrate the possibility of manipulating quantum states. Our results show that the optimal control of photon-assisted inter-ring transitions can be achieved by employing cascade-type and $\Lambda$-type transition mechanisms. Under chirped pulse impulsions, a robust and complete transfer of an electron to the final state is shown to coincide with the estimation of the Landau-Zener formula.Comment: RevTex, 9 pages, 5 figure

Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

The surface of proteins is heterogeneous with sophisticated but precise hydrophobic and hydrophilic patches, which is essential for their diverse biological functions. To emulate such distinct surface patterns on macromolecules, we used rigid spherical synthetic dendrimers (polyphenylene dendrimers) to provide controlled amphiphilic surface patches with molecular precision. We identified an,. I optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ads). Patchy dendrimers bound to the surface of Ads formed a synthetic polymer corona that greatly altered various host interactions of Ads as well as in vivo distribution. The dendrimer corona (1) improved the ability of Ad5-derived gene transfer vectors to transduce cells deficient for the primary Ad5 cell membrane receptor and (2) modulated the binding of Ads to blood coagulation factor X, one of the most critical virus host interactions in the bloodstream. It significantly enhanced the transduction efficiency of Ad5 while also protecting it from neutralization by natural antibodies and the complement system in human whole blood. Ads with a synthetic dendrimer corona revealed profoundly altered in vivo distribution, improved transduction of heart, and dampened vector sequestration by liver and spleen. We propose the design of bioactive polymers that bind protein surfaces solely based on their amphiphilic surface patches and protect against a naturally occurring protein corona, which is highly attractive to improve Ad5-based in vivo gene therapy applications

Interpersonal prosodic correlation in frontotemporal dementia.

Communication accommodation describes how individuals adjust their communicative style to that of their conversational partner. We predicted that interpersonal prosodic correlation related to pitch and timing would be decreased in behavioral variant frontotemporal dementia (bvFTD). We predicted that the interpersonal correlation in a timing measure and a pitch measure would be increased in right temporal FTD (rtFTD) due to sparing of the neural substrate for speech timing and pitch modulation but loss of social semantics. We found no significant effects in bvFTD, but conversations including rtFTD demonstrated higher interpersonal correlations in speech rate than healthy controls

Ground-Based Centimeter, Millimeter, and Submillimeter Observations of Recent Comets

Comets provide important clues to the physical and chemical processes that occurred during the formation and early evolution of the Solar System, and could also have been important for initiating prebiotic chemistry on the early Earth [I]. Comets are comprised of molecular ices, that may be pristine interstellar remnants of Solar System formation, along with high-temperature crystalline silicate dust that is indicative of a more thermally varied history in the protosolar nebula [2]. Comparing abundances of cometary parent volatiles, and isotopic fractionation ratios, to those found in the interstellar medium, in disks around young stars, and between cometary families, is vital to understanding planetary system formation and the processing history experienced by organic matter in the so-called interstellar-comet connection [3]. In the classical picture, the long-period comets probably formed in the nebular disk across the giant planet formation region (5-40 AU) with the majority of them originating from the Uranus-Neptune region. They were subsequently scattered out to the Oort Cloud (OC) by Jupiter. The short-period comets (also known as ecliptic or Jupiter Family Comets - JFC) reside mainly in the Edgeworth-Kuiper belt where they were formed. Given the gradient in physical conditions expected across this region of the nebula, chemical diversity in this comet population is to be expected [4,5]. We have conducted observations of comets I 03P/Hartley 2 (JFC) and C/2009 PI (Garradd) (OC), at primarily millimeter and submillimeter wavelengths, to determine important cosmogonic quantities, such as the ortho:para ratio and isotope ratios, as well as probe the origin of cometary organics and if they vary between the two dynamic reservoirs

Ground-Based Centimeter, Millimeter, and Submillimeter Observations of Comet 103P/Hartley 2

Comets provide important clues to the physical and chemical processes that occurred during the formation and early evolution of the Solar System, and could also have been important for initiating prebiotic chemistry on the early Earth [1]. Comets are comprised of molecular ices, that may be pristine interstellar remnants of Solar System formation, along with high-temperature crystalline silicate dust that is indicative of a more thermally varied history in the protosolar nebula [2]. Comparing abundances of cometary parent volatiles, and isotopic fractionation ratios, to those found in the interstellar medium, in disks around young stars, and between cometary families, is vital to understanding planetary system formation and the processing history experienced by organic matter in the so-called interstellar-comet connection [3]. We have conducted observations, at primarily millimeter and submillimeter wavelengths, where molecular emission is easily resolved, towards comets to determine important cosmogonic quantities, such as the ortl1o:pal'a ratio and isotope ratios, as well as probe the origin of cometary organics. Comets provide important clues to the processes that occurred during the formation and early evolution of the Solar System. Past observations, as well as laboratory measurements of cometary material obtained from Stardust, have shown that comets appear to contain a mixture of the products from both interstellar and nebular chemistries. A major observational challenge in cometary science is to quantify the extent to which chemical compounds can be linked to either reservoir