CHEM2601: Chemistry of Biologically Important

Molecules
Course Organizer: Prof S Howorka

Lecturers: Prof A Tabor, Prof Erik Arstad and Prof S Howorka

Normal prerequisite: CHEM1603 or CHEM1201

Units: 1/2 unit

Aims

The aim of the course is to cover in depth the chemistry of three major classes of biologically
important molecules; carbohydrates, peptides and proteins, and nucleic acids. In addition, the
course will provide an introduction to molecular imaging and cover methods for labelling of
biomolecules with fluorescent dyes and radionuclides. The course is aimed at second year
Biological Sciences and certain Natural Science students, and some knowledge of organic
chemistry is assumed; a pass in CHEM1201 or CHEM1603 is therefore a prerequisite. It is
not available for Chemistry students.

Objectives

• To know the structure, conformation and stereochemistry of the carbohydrates, and to

understand the chemical reactivity of mono-and di-saccharides.
• To recognise the structure and conformational properties of amino acids, peptide and
proteins. To understand strategies and methods for the chemical synthesis of native
and labelled proteins.
• To understand the relationships between structure and conformation of nucleic acids;
to understand the chemical reactivity of nucleic acids, and to gain insight into how
chemical reactivity affects the biological properties of nucleic acids.
• To appreciate the underlying principles for imaging with optical and nuclear
techniques, and to understand in depth the methods for labelling of biomolecules. To
know how radionuclides are produced, their radioactive decay properties and their
applications for imaging

Course Structure

• Lectures:24 hours
• Tutorials:0 workshops
• Labs:0

Assessment

• Exam: 80 % (2 hours)
• Lab: 0 %
• Coursework: one in-class test 20%

Recommended Texts
Carbohydrates

• B.G. Davis and A. J. Fairbanks, “Carbohydrate Chemistry", (Oxford Chemistry

Primer), Oxford University Press.
• P Collins and R Ferrier, "Monosaccharides, Their Chemistry and Their Roles in
Natural Products", Wiley, Chichester, 1995.

Nucleic Acids

• http://www.atdbio.com/nucleic-acids-book

• G M Blackburn, M J Gait, D Loakes, D M Williams, "Nucleic Acids in Chemistry

and Biology", 3rd ed, Royal Society of Chemistry, 2005.
• J D Watson et al, "Molecluar Biology of the Gene", 5th ed, Pearson Benjamin
Cummings, chapter 6, p 97-128, chapter 9, p235-258, CD-ROM with useful structural
tutorials, 2004
• B Alberts et al "Molecular Biology of the Cell", 4th edition, Garland Science, chapter
5, p 267-275, 2002

Peptides

• P Bailey, "An Introduction to Peptide Chemistry", Wiley, 1990.

• J Jones, "Amino Acid and Peptide Synthesis", (Oxford Chemistry Primer), Oxford
Scientific, 1984.
• S Doonan , “Peptides and Proteins”, Royal Society of Chemistry, 2002
• D L Nelson, M M Cox, Lehninger Principles of Biochemistry , 4th Edn., Worth, New
York, 2005

Imaging

• Sampson's Textbook of Radiopharmacy, 4th Ed, Pharmaceutical Press, 2011.

• Miller et al. (2008), Synthesis of 11C, 18F, 15O, and 13N Radiolabels for Positron
Emission Tomography, Angew. Chem. Int. Ed., 47, 8998 - 9033.
• Ashley M Groves AM, Win T, Haim SB, Ell PJ (2007). Lancet Oncol., 8: 822-30.
• http://www.invitrogen.com/site/us/en/home/support/Tutorials.html
• Luke D. Lavis and Ronald T. Raines (2008), Bright Ideas for Chemical Biology, ACS
Chemical Biology, 3(3): 142-155.

Course Outline

Peptides and Peptidomimetics: SH, 6 lectures

Overview of amino acids, structure and physical properties. Chemical synthesis of amino
acids. Amino acid protecting groups. Reagents for forming peptide bonds. Chemical
synthesis of peptides using solution and solid-phase methods. Combinatorial libraries of
peptides. Labelling of peptides with dyes and other markers.

Molecular Imaging : EA, 5 lectures

Introduction to biomedical imaging methods with a focus on optical and nuclear techniques.
Principles of fluorescent imaging and photophysical properties of fluorescent dyes. Methods
for conjugation of fluorescent dyes to biomolecules and biological applications. Introduction
to radiochemistry, production of radionuclides, radioactive decay and types of ionizing
radiation. Methods for radiolabelling of carbohydrates, nucleic acids, small molecules,
peptides and proteins. Application of radiotracers for biomedical imaging.

Carbohydrates: AT, 6 lectures

Introduction to carbohydrates and their biological significance. Classification. Open chain

and ring structures of monosaccharides. Recap of organic stereochemistry. Diagrammatic
representations of carbohydrates. Hemiacetal formation. Mutarotation. Anomeric Effect,
Fischer glycosylation, Reaction of glycosides with acetone and acid.
Reactions of monosaccharides: oxidation and reduction of the carbonyl group, reactions at
the anomeric centre – glycoside formation. Anomeric effect. Reactions of hydroxyl groups:
esterification, ether and acetal formation and their applications as protecting groups.

Nucleic Acids SH, 7 lectures Examples of nucleic acids and evolutionary aspects, structure
and conformation of nucleotides and oligonucleotides. Relationship between nucleotide
conformation and tertiary structure of DNA and RNA. Deviations from ideal structures.
Mismatches and mutagenesis. Triple helices. Structure and biological properties of modifies
oligonucleotides.
Interactions of small molecules with DNA. Non-covalent binding: electrostatic, minor
groove, intercalation, biological consequences. Covalent binding: alkylating agents,
metabolically activated alkylating agents. Free radical and photochemical damage to DNA.
Anticancer drugs and environmental mutagens. Biological consequences of DNA damage;
DNA repair enzymes.