Aims

To provide an overview of the methods and approaches used in modern chemical biology and drug discovery.
To introduce key concepts and techniques in chemical biology, including Synthesis of DNA, RNA and peptides
To introduce key concepts and techniques in drug discovery. To discuss the methods used in key stages of a project i.e. target identification and validation, hit discovery, hit validation, hit-to-lead optimisation and lead optimisation.

Outline Of Syllabus

Chemical Biology and Drug Discovery
The discovery of new drugs to treat unmet needs of patients is a global undertaking. This module
covers modern topics in drug discovery e.g., target validation, hit identification and the pre-clinical optimisation of drugs. Theoretical concepts and experimental methods will be discussed in detail. The underpinning chemical biology methods will be described in detail, focusing on how chemical biology interlinks with drug discovery. Recent literature is used to illustrated with case studies from recent discovery projects.

Methods in Drug Discovery
Dr IR Hardcastle
List of topics covered:
Overview of drug discovery and drug targets
Peptide synthesis and peptide libraries
Target validation methods (siRNA)
Hit identification technologies - Building assay cascades
Fragment-based drug discovery - Biophysical testing
DNA-encoded libraries
Phenotypic drug discovery - Target deconvolution
Cell based assays
Chemical probes vs drugs
Small-molecule library synthesis strategies (parallel synthesis)
Hit-to-lead strategies and methods
Lead optimisation - challenges
Lead optimisation - in vitro and in vivo DMPK
Targeted protein degradation – using cellular machinery and chemistry to act on protein of interest (PROTAC, DUBTAC, LYTAC, etc etc)

Fundamentals of Chemical Biology
1.       Nucleotide chemistry / applications
a.       DNA/RNA Chemical synthesis. Chemical modifications,
b.       Biosynthetic methods
c.       Research Applications – NGS, DELs, aptamers, etc
2.       Proteins and biochemical/biophysical characterisation
a.       Molecular cloning, SDM,
b.       Protein characterisation
c.       Crystallography (in a bit more depth) and design / mutations
d.       Conformational changes (NMR, CD, other techniques)
e.       Evolving enzymes as efficient biocatalysts
3.       Bioconjugation
a.       How to modify proteins and biomolecules
b.       Click chemistry
c.       Photochemistry
4.       Peptide chemistry and unnatural amino acids
5.       Carbohydrate chemistry

Teaching Rationale And Relationship

Key concepts and supporting examples are delivered by online teaching materials and in person lectures. Seminars are used to provide practice questions and give assessment feedback.

Assessment Rationale And Relationship

The summative coursework exercise will assess the students’ ability to understand and apply their learning to relevant literature case studies in drug discovery and chemical biology.
The summative online exam will test key concepts, definitions and examples across the taught material.
The formative coursework exercise will assess and provide feedback on the students’ ability to communicate their understanding and applied learning with a relevant literature case study in drug discovery.