Cyclopentadiene as a Multifunctional Reagent for Normal- and Inverse-Electron Demand Diels-Alder Bioconjugation.

Optimizing the Diels-Alder (DA) reaction for aqueous coupling has resulted in practical methods to link molecules such as drugs and diagnostic agents to proteins. Both normal electron demand (NED) and inverse electron demand (IED) DA coupling schemes have been employed, but neither mechanism entails a common multipurpose reactive group. This report focuses on expanding the bioconjugation toolbox for cyclopentadiene through the identification of reactive groups that couple through NED or IED mechanisms in aqueous solution. Dienophiles and tetrazine derivatives were screened for reactivity and selectivity toward antibodies bearing cyclopentadiene amino acids to yield bioconjugates. Twelve NED dienophiles and four tetrazine-based IED substrates were identified as capable of practical biocoupling. Furthermore, tetrazine ligation to cyclopentadiene occurred at a rate of 3.3 ± 0.5 M-1 s-1 and was capable of bioorthogonal transformations, as evidenced by the selective protein labeling in serum. Finally, an antibody-drug conjugate (ADC)-bearing monomethyl auristatin E was prepared via tetrazine conjugation to cyclopentadiene. The resulting ADC was stable and demonstrated potent activity in vitro. These findings expand the utility of cyclopentadiene as a tool to couple entities to proteins via dual DA addition mechanisms.

Measuring Atmospheric CO2 Enhancements From the 2017 British Columbia Wildfires Using a Lidar.

During the summer 2017 ASCENDS/ABoVE airborne science campaign, the NASA Goddard CO2 Sounder lidar overflew smoke plumes from wildfires in the British Columbia, Canada. In the flight path over Vancouver Island on 8 August 2017, the column XCO2 retrievals from the lidar measurements at flight altitudes around 9 km showed an average enhancement of 4 ppm from the wildfires. A comparison of these enhancements with those from the Goddard Global Chemistry Transport model suggested that the modeled CO2 emissions from wildfires were underestimated by more than a factor of 2. A spiral-down validation performed at Moses Lake airport, Washington showed a bias of 0.1 ppm relative to in situ measurements and a standard deviation of 1 ppm in lidar XCO2 retrievals. The results show that future airborne campaigns and spaceborne missions with this type of lidar can improve estimates of CO2 emissions from wildfires and estimates of carbon fluxes globally.