Principles of Medicinal Chemistry

Overview

Summary of lecture content

Introduction to Medicinal Chemistry (7 Lectures/ 1 Seminar):
This course will introduce the key concept of medicinal chemistry, and underpin student’s learning for their subsequent medicinal chemistry topics/modules.
 Protein-drug interactions.
 Introduction to small molecule metabolism.
 Toxicity and toxic alerts
 Hit to Lead and Lead optimisation.
 Assay development and Use

Targets and proteins (Dr Joe Vyle 11 Lectures and 1 Seminar)
Basic methodologies (5 Lectures):
• DNA synthesis / amplification.
• Chemical Synthesis.
• Enzymatic synthesis.
• Amplification by PCR.
• Epigenetic modifications of DNA.
Target Identification and Validation (6 Lectures):
• Genomics approaches
o mRNA knockdown
o RNA amplification.
o Quantification by QPCR.
o RNA interference / CRISPR/ CAS9.
• DNA and DNA modification analysis:
o Sequencing
 Chemical (Maxam-Gilbert);
 Enzymatic (Sanger)
 New methodologies.
• Proteomics
o Mass spectrometry;
o Side-chain modification (+ MS identification)
 Isoforms phosphorylation / ubiquitination / palmitoylation / glycosidation
 Covalent drug-target interactions

Modelling and Drug Development (Dr Meilan Huang, 10 lectures and 1 Seminar)
• QSAR (3 lectures):
• Quantitative Structure Activity Relationships (QSAR):-Hydrophobicity, electronic & steric factors (Taft and Hammett relationships)
• QSAR analysis (Craig plots, Topliss schemes, Hansch analysis),
• 3D-QSAR
•
Bioisosterism(3 lectures):
• Isosterism and Bioisosterism
• Peptidomimetics

Fragment based drug design (4 lectures)
• Drug Design: protein structure prediction, protein-ligand docking methods, structure-based drug design, ligand-based drug design,
• Focused combinatorial library design
• Protein-protein interactions.

Learning Objectives

Upon completion of this module, the students
• will have gained a general understanding of the process underlying drug discovery ranging from biological (target identification) to chemical (chemical structure optimisation) issues.
• The students will also have been exposed to examples of and the application of synthetic organic chemistry used for total synthesis of biologically-relevant target molecules and the sites and mechanisms of drug action.

Skills

Skills associated with the module:

Learners are expected to demonstrate the following on completion of the module:
• Subject specific skills in the context of medicinal chemistry in addition to problem-solving skills related to drug design and drug discovery.

Assessment