Design, synthesis, conjugation and reactivity of novel trans,trans-1,5-cyclooctadiene-derived bioorthogonal linkers

Funding Information: The authors thank Irene Feiner, Marion van Leeuwen-Chomet, and Joey Muns for their helpful insight. We acknowledge financial support from the University of Aberdeen and European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 675417.Peer reviewedPostprin

A comparative study of electrical and optical properties of InN and In0.48Ga0.52N

We present results of our studies concerning electrical and optical properties of In0.48Ga0.52N and InN. Hall measurement were carried out at temperatures between T=77 and 300 K. Photoluminescence (PL) spectrum in InN and In0.48Ga0.52N. InN has a single peak at 0.77 eV at 300 K. However, the PL in In0.48Ga0.52N has two peaks; a prominent peak at 1.16 eV and a smaller peak at 1.55 eV. These two peaks are attributed to Indium segregation corresponding to a high Indium concentration of 48% and a low concentration of 36%. High electric field measurements indicate that drift velocity that tends to saturate at around Vd=1.0×107 cm/s at 77 K in InN at an electric field of F=12 kV/cm. However, in In0.48Ga0.52N the I–V curve is almost linear up to an electric field of F=45 kV/cm, where the drift velocity is Vd=1.39×106 cm/s. At applied electric fields above this value a S-type negative differential resistance (NDR) is observed leading to an instability in the current and to the irreversible destruction of the sample

Adolescenti e self-cutters: analisi di una popolazione

Nonsuicidal self-injury (NSSI), defined as the deliberate destruction of body tissue without suicidal intent, is a multifaceted phenomenon among adolescents as well as representing a major health issue in this age. A better understanding of self-injury comorbidities is therefore crucial to improve our knowledge in terms of assessment, treatment and prevention. A review of 23 self harming patientsIt is presented

Design, synthesis, conjugation and reactivity of novel trans,trans-1,5-cyclooctadiene-derived bioorthogonal linkers

The tetrazine/trans-cyclooctene (TCO) inverse electron-demand Diels–Alder (IEDDA) reaction is the fastest bioorthogonal “click” ligation process reported to date. In this context, TCO reagents have found widespread applications; however, their availability and structural diversity is still somewhat limited due to challenges connected with their synthesis and structural modification. To address this issue, we developed a novel strategy for the conjugation of TCO derivatives to a biomolecule, which allows for the creation of greater structural diversity from a single precursor molecule, i.e., trans,trans-1,5-cyclooctadiene [(E,E)-COD] 1, whose preparation requires standard laboratory equipment and readily available reagents. This two-step strategy relies on the use of new bifunctional TCO linkers (5a–11a) for IEDDA reactions, which can be synthesized via 1,3-dipolar cycloaddition of (E,E)-COD 1 with different azido spacers (5–11) carrying an electrophilic function (NHS-ester, N-succinimidyl carbonate, p-nitrophenyl-carbonate, maleimide) in the ω-position. Following bioconjugation of these electrophilic linkers to the nucleophilic residue (cysteine or lysine) of a protein (step 1), the resulting TCO-decorated constructs can be subjected to a IEDDA reaction with tetrazines functionalized with fluorescent or near-infrared (NIR) tags (step 2). We successfully used this strategy to label bovine serum albumin with the TCO linker 8a and subsequently reacted it in a cell lysate with the fluorescein-isothiocyanate (FITC)-derived tetrazine 12. The same strategy was then used to label the bacterial wall of Gram-positive Staphylococcus aureus, showing the potential of these linkers for live-cell imaging. Finally, we determined the impact of structural differences of the linkers upon the stability of the bioorthogonal constructs. The compounds for stability studies were prepared by conjugation of TCO linkers 6a, 8a, and 10a to mAbs, such as Rituximab and Obinutuzumab, and subsequent labeling with a reactive Cy3-functionalized tetrazine