Nobel Prize lecture: Morten Meldal, Nobel Prize in Chemistry 2022

The speaker, a Danish native and professor at the University of Copenhagen, begins by expressing gratitude to the giants in the field of chemistry, including Klaus Bach, Huskin, Woodward, and others, for their contributions to NMR structural studies, psychoedition reactions, and quantum chemistry. He acknowledges the support of the Nobel Foundation, the Royal Swedish Academy of Sciences, and his colleagues and family, highlighting the importance of nature and chemistry in his life and education. He emphasizes the need for chemistry to address global challenges and the importance of inspiring young people to learn chemistry.

The speaker recounts his academic and research journey, starting with his work on carbohydrates and peptides at Carlsberg Laboratory. He describes the establishment of the spark Center, funded by the Danish national Research Foundation, to focus on quantitative chemical reactions. The speaker introduces combinatorial chemistry, explaining the process and its exponential potential for generating compounds. He also discusses the development of a method for synthesizing difficult peptides and the discovery of the copper-catalyzed azide-alkyne cyclization reaction, which laid the foundation for click chemistry.

The speaker elaborates on the versatility of click chemistry, highlighting its compatibility with various biomolecules and its potential applications in pharmaceutical and material sciences. He presents a hypothetical example of using click chemistry to create a compound that can target and kill cancer cells through apoptosis. The speaker also explains the 'toolbox' concept, comparing the limited number of clean and efficient reactions available in click chemistry to the broader, less environmentally friendly methods used in other fields.

The speaker discusses the application of click chemistry in creating enzyme inhibitors and activating melanocortin receptors, which are involved in various physiological processes including obesity. He describes the process of identifying active compounds through combinatorial libraries and the discovery of a potent inhibitor against a specific protease. The speaker also explains how click chemistry enabled the cyclization of peptides to create compounds with high receptor activity, offering potential avenues for treating obesity.

The speaker explores the use of click chemistry in creating antimicrobial peptides inspired by the Japanese horseshoe crab's immune system. He details the process of replacing disulfide bonds with triazoles to create cyclic peptides that effectively kill bacteria. Additionally, the speaker discusses the challenges of expressing proteases and how click chemistry was used to assemble two halves of a protease, resulting in a fully active enzyme.

In the final part of the script, the speaker emphasizes the role of serendipity in scientific discovery and the importance of allowing researchers the freedom to explore unexpected findings. He suggests that funding should be more flexible, based on recent performance, to encourage creativity and exploration. The speaker concludes by advocating for chemistry education from an early age, using visual aids to inspire future generations of chemists.

The speaker concludes the presentation with heartfelt thanks to his mentors, colleagues, and family for their support throughout his career. He acknowledges the contributions of Christian Tony and Klaus Spock, as well as the Danish national Research Foundation and Carl.