news & views balance between lipophilicity and charge the imine methide by-product resulting conjugates in general, is highly welcomed distribution. In a previous application5 from the linker self-immolation deserves and will certainly spur further studies in by the same group of researchers, an a comprehensive toxicological study the future. ❐ antibody–rifabutin conjugate was shown given its similarity to quinone methides, to be superior to vancomycin in vivo, which are members of the so-called Tiago Rodrigues and Gonçalo J. L. Bernardes are at suggesting that antibody–antibiotic pan assay interference compounds6 — a the Instituto de Medicina Molecular, Faculdade de conjugates are viable for enriching the group of molecules containing dreaded Medicina, Universidade de Lisboa, Av. Prof. Egas current therapeutic armamentarium. substructures that are notorious for their Moniz, 1649-028 Lisboa, Portugal. G. J. L. B. is As the team recognize, this is not a uncontrolled polypharmacology and also in the Department of Chemistry, University of universal solution for drug delivery and a associated toxicity. That said, despite the Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. more comprehensive number of drugs and nucleophile acceptor potential of the imine e-mail: [email protected]; protein carriers will need to be assessed. methide motif, and any possible toxicity [email protected] Despite the potential to enrich the current profile, it may still be compatible with chemistry toolbox in chemical biology, the delivery of drugs for a disease — for References 1. Chudasama, V., Maruani, A. & Caddick, S. Nat. Chem. there are several important pending instance, if the therapeutic benefit is high, 8, 114–119 (2016). questions, including the suitability of the or if this approach enables a lower dose of a 2. Rodrigues, T., Reker, D., Schneider, P. & Schneider, G. technology to expand the tractable drug cytotoxic drug to be used. Nonetheless, this Nat. Chem. 8, 531–541 (2016). space and address unmet medical needs in report represents a disclosure that promises 3. Staben, L. R. et al. Nat. Chem. 8, 1112–1119 (2016). 4. Burke, P. J. et al. Mol. Cancer Ther. 15, 938–945 (2016). other disease areas, such as inflammation to enable the inclusion of new drugs in 5. Lehar, S. M. et al. Nature 527, 323–328 (2015). and immunomodulation. Moreover, the realm of antibody– and carrier–drug 6. Baell, J. B. & Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010).
2016 NOBEL PRIZE IN CHEMISTRY Molecular machines In what has been a giant leap forward for fundamental chemistry, researchers have spent the past two decades creating tiny machines that can perform tasks in response to external stimuli. These machines can synthesize or transport PRISCHING JAMES small molecules, and some have been shown to come together in large numbers to accomplish macroscopic work such as
making objects bend, rotate or contract. IMAGES /GETTY HERTZOG PATRICK In recognition of their pioneering efforts in this field, Jean-Pierre Sauvage,
Fraser Stoddart and Ben Feringa (left to / UNIV OF STRASBOURG SCHRÔDER CATHERINE right) have been jointly awarded the 2016 Nobel Prize in Chemistry “for the design and synthesis of molecular machines”. the tools they needed to build nanoscale 360° rotation in a single direction by The first real breakthrough came in machines — molecules with moveable photoisomerization of the double bond 1983 when Jean-Pierre Sauvage, from parts that undergo reversible, positional through which they are connected. the University of Strasbourg, devised displacements. The next step was to Feringa has since introduced reversible a high-yielding metal-templated gain motional control, which they each directionality to his motor and increased strategy to synthesize a catenane: achieved in 1994 when they introduced the rotational frequency to over 12 MHz. an assembly of two molecular rings chemically distinct redox-active units into His group also synthesized a molecule that are mechanically interlocked but these systems and controlled the relative based on four rotors that can propel can move freely with respect to one positions of catenane or rotaxane rings itself across a surface in a straight line another. In 1991, Fraser Stoddart, now at using electrochemistry. Between them in response to electronic excitation. The Northwestern University, was responsible they have since developed molecular development of molecular motors has for the next major development: muscles, logic gates, elevators and led to enormous progression in the field, a rotaxane shuttle consisting of a pumps, with Stoddart in particular having with researchers now designing machines macrocyclic ring that can move between contributed significantly to the catalogue that function in high-energy states away two different ‘stations’ along the axle of available machinery. from equilibrium — a state completely component on which it is threaded, Ben Feringa from the University of familiar to the biologist, but one that trapped there by virtue of a bulky stopper Groningen made significant contributions was relatively uncharted territory for at each end. to the design of rotary molecular motors. the chemist. By creating entangled assemblies, In 1999 his team reported a molecule Sauvage and Stoddart were armed with that possesses two blades that undergo VICTORIA RICHARDS
1090 NATURE CHEMISTRY | VOL 8 | DECEMBER 2016 | www.nature.com/naturechemistry ©2016 Mac millan Publishers Li mited, part of Spri nger Nature. All ri ghts reserved.