New therapeutics with robust C1 photo-linchpins
- Reference number
- ID20-0089
- Project leader
- Lindberg Martín-Matute, Belen
- Start and end dates
- 210901-260831
- Amount granted
- 2 500 000 SEK
- Administrative organization
- Stockholm University
- Research area
- Life Sciences
Summary
The purpose of this project is to develop reagents and methods to create robust linkages in small and large molecules using the most fundamental organic linker: a single carbon atom. Main Objectives - Synthesis of new C1 linchpin reagents with different properties - Evaluate and develop orthogonal coupling reactions with these reagents in medicinal compounds - Gain deeper fundamental understanding on the photo-activation of the reagents - Explore photo-biocatalytic conjugation methods using enzymes in-vitro and in-vivo. - Development of medicinal conjugates in automatized robotic high-throughput experimentation (HTE) platforms. Work-plan Month 1-18 - Compulsory PhD courses and fundamental studies at SU Month 19-48 - HTE and Chemical Biology applications at AZ Expected results - Automatic synthesis of medicinal conjugates and medicinal probe molecules for R&D - Light activation of drugs - In-vivo selective coupling reactions - Fast isotopic labelling of drug candidates
Popular science description
Medicine is evolving into a future in which patients will receive medicines that are specifically designed and developed for them. These drugs will be assembled from various parts by using some atoms to hold the structure together. At the moment these connecting atoms, are often substantially large, rigid, and complicated structures and they can affect the way the drug finds its way and interacts with its target in the body. The smallest unit that can be designed to replace this large connections are single carbon atoms, which in comparison are a single point and therefore way more flexible, yet very strong and less likely to degrade. The chemical reaction that we will use to create this single carbon atom connections will use chemicals that are already exist in the healthy body and blue light. This means that the reaction will not be toxic to living organisms and will be activated whenever required using external light stimuli. These features, will allow to use this reaction to activate drugs, or study the way they work in the body or the cell. Also, the simplicity of this approach is good to teach robots how to do these reactions automatically. This is important because robots could then prepare and test drugs without rest and find the right drug for the right patient much faster than ever before. The small connections using single carbon atoms will have a minimal effect in the function of the different active parts of the drug, thus enhancing the chances that more of the candidates prepared by the robot will be therapeutically effective.