Again, background is initially high, but this background is inactive. field, outlining emerging areas and important difficulties to overcome. Introduction Although chemists have been making molecules that interact with life since the dawn of modern chemistry, the actual chemical reactions used to assemble the molecules were kept as far away from life as possible. They were performed in organic solvents where water, and often oxygen, were to be avoided. Impurities were anathema. This all changed with the introduction of bioorthogonal chemistry by Bertozzi and co-workers.1?3 The concept is elegant. Can we design reactions that are so selective they can be performed reliably even in a complex biological environment? SB-408124 These reactions must proceed efficiently in the presence of the multitude of functional groups found in Rabbit Polyclonal to OR2AT4 living systems such nucleophiles, electrophiles, reductants, oxidants, and of course the solvent of life water. Simultaneously, these reactions should have a minimal impact on the biology itself. The transformation bioorthogonal chemistry brought on in the field of chemical biology was monumental. All of a sudden, reactions that previous generations performed in refluxing toluene, were now being carried out in an aqueous mixture of proteins and sugars. Malignancy cells and zebrafish replaced round-bottom flasks.4,5 Bioorthogonal reactions have already made a tremendous scientific impact, helping us understand glycosylation in cells and animals,6 providing tools for conjugating functional groups to therapeutically relevant proteins such as antibodies,7 and enabling the assembly of molecular imaging agents in vivo to detect disease.8 The concept of bioorthogonal chemistry has inspired a generation of chemical biologists to think about how vintage organic reactions can be performed in concert with living systems and how such reactions could lead to the development of tools to help understand biology. I think one of the greatest contributions of bioorthogonal chemistry has been its ability to challenge our imagination regarding the kinds of reactions that can be performed in living systems and how this enables us to ask extremely interesting and ambitious questions. Can pharmaceuticals be synthesized inside humans?9 Can we co-opt bioorthogonal reactions to detect metabolites in situ?10 How many orthogonal reactions can be performed simultaneously?11 Over the last several years, our ability to combine chemistry and biology has accelerated through improved tools and resources. Therefore, I believe there are numerous future prospects for how bioorthogonal chemistry will have an increasing impact on chemical biology and medicine. In this short Outlook, I will describe my opinion of the future of bioorthogonal chemistry and explore what I believe are some outstanding opportunities in the field. I also outline many of the challenges that will need to be overcome for some of these opportunities to be realized. The Development of New Bioorthogonal Reactions Undoubtedly there will be continued development of new bioorthogonal reactions. Bioorthogonal chemistry has encouraged chemists to consider how a vast number of organic transformations might be adapted to work in living systems. In just the last year alone, there has been the introduction of several new bioorthogonal reactions.12?15 However, while there are a multitude of possible reactions that could be developed into bioorthogonal processes, it is worthwhile pointing out some of the desired properties of new bioorthogonal reactions that would significantly advance the field. For instance, the continued development of very rapid bioorthogonal reactions is desirable. Rapid reactions are useful because they, in.The predictions I have outlined are obviously just a small part of the future of bioorthogonal chemistry. Indeed, I am confident that some of the most exciting applications will come as a surprise and be driven by the need to address pressing biological and medical problems. toward these goals is to be made. Given the incredible past successes of bioorthogonal chemistry and the rapid pace of innovations in the field, the future is undoubtedly very bright. Short abstract Bioorthogonal reactions have found widespread use in chemical biology. This article gives a brief outlook on the future of the field, outlining emerging areas and key challenges to overcome. Introduction Although chemists have been making molecules that interact with life since the dawn of modern chemistry, the actual chemical reactions used to assemble the molecules were kept as far away from life as possible. They were performed in organic solvents where water, and often oxygen, were to be avoided. Impurities were anathema. This all changed with the introduction of bioorthogonal chemistry by Bertozzi and co-workers.1?3 The concept is elegant. Can we design reactions that are so selective they can be performed reliably even in a complex biological environment? These reactions must proceed efficiently in the presence of the multitude of functional groups found in living systems such nucleophiles, electrophiles, reductants, oxidants, and of course the solvent of life water. Simultaneously, these reactions should have a minimal impact on the biology itself. The SB-408124 transformation bioorthogonal chemistry triggered in the field of chemical biology was monumental. Suddenly, reactions that previous generations performed in refluxing toluene, were now being done in an aqueous mixture of proteins and sugars. Cancer cells and zebrafish replaced round-bottom flasks.4,5 Bioorthogonal reactions have already made a tremendous scientific impact, helping us understand glycosylation in cells and animals,6 providing tools for conjugating functional groups to therapeutically relevant proteins such as antibodies,7 and enabling the assembly of molecular imaging agents in vivo to detect disease.8 The concept of bioorthogonal chemistry has inspired a generation of chemical biologists to think about how classic organic reactions can be performed in concert with living systems and how such reactions could lead to the development of tools to help understand SB-408124 biology. I think one of the greatest contributions of bioorthogonal chemistry has been its ability to challenge our imagination regarding the kinds of reactions that can be performed in living systems and how this enables us to ask extremely interesting and ambitious questions. Can pharmaceuticals be synthesized inside humans?9 Can we co-opt bioorthogonal reactions to detect metabolites in situ?10 How many orthogonal reactions can be performed simultaneously?11 Over the last several years, our ability to combine chemistry and biology has accelerated through improved tools and resources. Therefore, I believe there are numerous future prospects for how bioorthogonal chemistry will have an increasing impact on chemical biology and medicine. In this short Outlook, I will describe my opinion of the SB-408124 future of bioorthogonal chemistry and explore what I believe are some outstanding opportunities in the field. I also outline many of the challenges that will need to be SB-408124 overcome for some of these opportunities to be realized. The Development of New Bioorthogonal Reactions Undoubtedly there will be continued development of new bioorthogonal reactions. Bioorthogonal chemistry has encouraged chemists to consider how a vast number of organic transformations might be adapted to work in living systems. In just the last year alone, there has been the introduction of several new bioorthogonal reactions.12?15 However, while there are a multitude of possible reactions that could be developed into bioorthogonal processes, it is worthwhile pointing out some of the desired properties of new bioorthogonal reactions that would significantly advance the field. For instance, the continued development of very rapid bioorthogonal reactions is desirable. Rapid reactions are useful because they,.