Molecular click adventures – A leap from the shoulders of giants
Nobel Laureate Morten Meldal, University of Copenhagen, Denmark
November 9, 2023, 12:00 p.m.
Auditorium between Buildings 2 and 3 and Zoom
Abstract
The concept of click chemistry matured simultaneously in different laboratories around the world in the 1990s. There was an urgent need for quantitative chemical reactions/molecular LEGO® to cope with the pressure from combinatorial science to synthesize, screen and identify one out of thousands – millions of compounds. We combined Peptide diversity with a variety of organic reactions including Diels Alder, Suzuki, INAIC and other reactions. During these investigations, we more or less serendipitously discovered the CuAAC click reaction in 2001. The mechanism of the reaction will be discussed and its application in a variety of studies involving immobilization, mimicry, structural control and protein ligation will be presented. Our investigations included the CuAAC reaction in the synthesis of stable surrogates for disulfide bonds in antibiotic 9; we produced a click protease with improved proteolytic activity and ligated the HIV fusion triple helix onto a fluorescent click template. The more existential aspects of our fundamental understanding of chemistry, the importance of serendipity to unravel the true complexity of our world at the molecular level, the associated need for freedom of research, and our pledge to the young to study chemistry for a better future will also be discussed.
