Nucleic Acids and Bioorganic Mechanisms
| Code | School | Level | Credits | Semesters |
| CHEM4026 | Chemistry | 4 | 10 | Spring UK |
- Code
- CHEM4026
- School
- Chemistry
- Level
- 4
- Credits
- 10
- Semesters
- Spring UK
Summary
Nucleic Acids: The module explores the structure, chemistry and molecular recognition of nucleic acids. Solid-phase methods for the synthesis of DNA and RNA oligonucleotides will be covered in detail. The chemical reactivity of DNA towards mutagens, carcinogens and ionising radiation and anti-tumour drugs is explored in mechanistic detail. The effects of free radicals in generating DNA lesions and leading to strand breaks will be described in detail alongside mechanistic studies of the mode of action of chemically reactive anti-tumour (ene-diyne) natural products. The structural features of the DNA double helix will be presented and mechanisms for recognition by non-covalent binding ligands will be discussed. Aspects of formation of the higher-order DNA triplex and quadruplex structures, selective ligand recognition, and RNA therapeutics (including RNA vaccines) will also be discussed.
Bioorganic Mechanisms: The chemistry of the coenzymes derived from vitamins is covered in detail including the biological importance, nutrition and deficiency diseases. Full mechanistic details are provided on reactions involving the coenzymes: Retinol, thiamine pyrophosphate, pyridoxal 5’-phosphate, cobalamin, flavins (FAD/FMN), nicotinamides (NAD(P)H, folic Acid, phylloquinone and pantothenic acid. Examples of mechanism-based inhibitors for a number of the enzymes are also described.
Target Students
MSci Chemistry OR MSci Medicinal and Biological Chemistry OR MSci Biochemistry and Biological Chemistry OR Natural Sciences AND Level 4 students.
Classes
- Two 1-hour lectures each week for 10 weeks
Assessment
- 100% Exam 1 (2-hour): Second re-assessment: If a further re-assessment is allowed by satisfying the conditions of Undergraduate Course Regulation 19, the form of the further re-assessment for this module will be 100% coursework.
Assessed by end of spring semester
Educational Aims
Nucleic Acids: Understand in depth the structure, chemistry and molecular recognition of nucleic acids and their reactivity towards mutagens, carcinogens, ionising radiation and anti-tumour drugs, and appreciate the mechanistic detail of how DNA bases can function as reactive nucleophiles. Appreciate the plasticity and dynamics of the DNA duple helix and its ability to present different molecular recognition features to small ligands that bind non-covalently. Understand how higher-order assemblies such as triplexes and quadruplexes can form and the essential structural and hydrogen bonding features of these assemblies. Bioorganic Mechanisms: Develop an understanding of the chemical reactivity of coenzymes and how these add significantly to the functionality of the 20 amino acids found in proteins. Relate the reactions previously studied in organic chemistry modules i.e. benzoin condensation, Baeyer-Villiger, borohydride-based reduction to their biological equivalents.Learning Outcomes
Knowledge and Understanding:
Nucleic Acids and Bioorganic Mechanisms
Students should have an understanding of:
1. The chemical reactivity and mechanisms of action of the coenzymes listed above.
2. How deficiency of the vitamins from which these coenzymes are derived impacts on humans and how inhibitors that operate on enzymes dependent on these coenzymes work.
3. The structure of DNA, nomenclature of nucleosides/nucleotides the biological processes of DNA transcription, replication, and translation.
4. Methods of DNA sequencing and solid-phase chemical synthesis.
5. Key aspects of DNA recognition by drug molecules that covalently or non-covalently bind DNA and the use of DNA and RNA in anti-gene and anti-sense strategies.
6. Understand and appreciate the dynamic nature of the DNA duple helix.
7. Base mutations and how these affect the genetic information.
8. The role of telomeres.
9. The chemical composition and mode-of-action of RNA vaccines.
Intellectual Skills:
Be able to:
1. Propose a reaction mechanism involving one or more of the coenzymes listed above
2. Propose a mechanism for a compound that has been identified to inhibit an enzyme dependent on these coenzymes and discuss the biological consequences.
3. Describe biological mechanisms and concepts
Transferable/Key Skills:
1. Problem-solving skills.