Topics to be Covered

Chapter 1. Structure, Nomenclature and Properties of Nucleic Acids

            Structure and nomenclature of bases, nucleosides, nucleotides

            Hybridization

            Aromaticity

            H-bonding

            Acid/Base properties

            Tautomerization

            Stability

            UV spectroscopy

            NMR spectroscopy

Chapter 2. Conformational Analysis of Nucleosides and Nucleotides

            Molecular mechanics

            Sugar pucker, envelope and twist forms

            Pseudorotation

            Other torsion angles

            Anomeric effect

Chapter 3. Conformational analysis of DNA duplexes, triplexes and quadruplexes, tRNA

            Base pairing motifs

            Watson Crick base pair

            Helical parameters

            A and B DNA duplexes

            Sequence-dependent variations in structure: Calladine’s rules

            Z DNA

            Triplexes

            Quadruplexes

Chapter 4. Thermodynamics of duplex formation

            Base pairing in water

            Pi-stacking in water

            Helix = coil equilibria

            helix initiation and propagation

            extracting thermodynamic parameters from melting temperature curves

            thermodynamics of RNA folding

Chapter 5. Chemical and Spectroscopic Probes of NA structure and Interactions

            Chemical probes

            2D NMR spectroscopy (NOESY and COSY)

Chapter 6. Small molecule – DNA interactions

            Intercalators

                        Ethidium bromide

                        Anthracyclines

                        echinomycin, triostin

            Minor groove binders

                        Distamycin/netropsin

                        Hoechst

                        bis-benzamide

                        polyamides

Chapter 7. Protein – DNA interactions

            protein secondary structure

            helix-turn-helix

            leucine zippers

            zinc fingers

            other motifs

Chapter 8. Supercoiling

            Circular DNA forms

            Electrophoresis

            knots and catenanes

            free energy of supercoiling

            driving structural transitions

            topoisomerases

Chapter 9. DNA bending

            Discovery of DNA bending

            Circular permutation assay

            Sequence-specificity of bending

            Determining bending and unwinding angles

            Determining bending direction

            Bending by assymetric charge neutralization

Chapter 10. Chemical synthesis of nucleic acids

            synthesis of nucleosides

            synthesis of nucleotides

Chapter 11. Solution and solid phase synthesis of DNA, RNA

Chapter 12. DNA chips, Chemical Synthesis of Modified nucleic acids

            2D photolithographic synthesis of DNA (DNA chips)

            thiolated DNA

            synthesis of peptide nucleic acids

Chapter 13. Enzymatic synthesis of nucleotides, de novo, salvage

Chapter 14. Enzymatic synthesis of DNA, RNA, and protein, PCR,

Chapter 15. Physical, chemical, and enzymatic sequencing of DNA and RNA

            Maxam Gilbert base-specific

            Sanger dideoxy

            Automated Sequencing with fluorescence detection

            Nucleases (RNA)

            Mass spectrometry

Chapter 16. In vitro evolution, SELEX, catalytic DNA, nucleic acid encoded tags

Chapter 17. Genetic engineering, site-directed mutagenesis

Chapter 18. Protein expression, unnatural mutagenesis, semi-synthetic proteins

Chapter 19. Photochemistry of DNA

            cyclobutane dimers

            cytosine hydrates

            (6-4) products

            Dewar isomers

            TA* photoproducts

            AA photoproducts

            sensitized reactions

Chapter 20. Radiation Chemistry

            Chemistry of ionizing radiation in water

            DNA strand cleavage

            DNA adducts

Chapter 21. Radiomimetic Agents, Footprinting and affinity cleaving

            bleomycin

            enediyne class

                        calicheamycin

                        esperamycin

                        neocarcinostatin

            MPE    footprinting      

            DE       affinity cleaving

            oligo-x (x=EDTA, enzyme, alkylator)

                        duplex (anti-sense)

                        triplex (anti-duplex)

            protein-X (x=EDTA, enzyme, alkylator)

Chapter 22. Covalent Binders/Xenobiotics

            AAF - carcinogen

            Aflatoxin - carcinogen

            BPDE - carcinogen

            anthramycin - toxin

            crosslinkers

                        mustards (chemical warfare and anticancer)

                        cis-platin (inorganic complex)

                        mitomycin (bioreductively activated, anticancer)

                        psoralen (phototoxin

Chapter 23. DNA Repair Enzymes

            Direct repair

            Glycosylases

            Excinucleases

Chapter 24. RNA cleavage chemistry

 

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