A "top down" approach to diverse small molecule scaffolds

Lead Research Organisation: University of Leeds
Department Name: Sch of Chemistry

Abstract

Historically, chemists' exploration of chemical space has been uneven and unsystematic. Most diversity-oriented approaches to expand the range of available molecular scaffolds have exploited a the "build-couple-pair" approach in which building blocks are linked and then cyclised to yield scaffolds. This iCASE project (with AstraZeneca) will develop a complementary "top down" approach in which complex, yet synthetically accessible, intermediates are simplified/developed to yield alternative molecular scaffolds. Specifically, cycloaddition chemistry will be developed and exploited in the synthesis of complex intermediates, which will then be transformed into alternative scaffolds by ring cleavage, annulation and ring expansion. The synthetic approach will be highly efficient, and will enable the synthesis of many diverse molecular scaffolds. The biological relevance of the novel scaffolds will be investigated in order to establish the value of the approach in driving bioactive small molecular discovery. The project focuses on the development of a new chemical approach to drive ligand discovery, and aligns with the EPSRC's chemical biology research area.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/P510555/1 30/09/2016 29/09/2021
1799563 Studentship EP/P510555/1 30/09/2016 29/09/2020 Chloe Elizabeth Townley
 
Description AstraZeneca Collaboration 
Organisation AstraZeneca
Department Oncology
Country United Kingdom 
Sector Private 
PI Contribution Experimental research into the top down approach to Lead-Oriented Synthesis (LOS) will be conducted during my time at Leeds
Collaborator Contribution My industrial supervisor offers support and guidence on the direction of the project as well as a 2 month placement at one of their R&D sites. Aside from placement they offer financial support through out my PhD.
Impact None as of yet
Start Year 2016
 
Description Astbury Conversation- public engagement event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact The Astbury conversation is an interdisiplinary event where GCSE school children and members of the general public are invited to attend an outreach workshop to learn about different areas across biology and chemistry. Our stall explained to concept of small bio active molecule discovery and this year focuses on Fragment based drug discovery. A game is used to explain the concept of small molecules binding into a target and how fragments can be grown into drugs.
Year(s) Of Engagement Activity 2018,2020