1Chapter 16 Nucleic acidsNucleic acids are biopolymers made of nucleotides, aldopentoses linked to a purine or pyrimidine and a phosphate.Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are the chemical carriers of genetic information.2Section 1 Classificationdeoxyribonucleic acids (DNA)ribonucleic acids (RNA)nucleic acidsRNAribosomal RNA (rRNA, 核蛋白体RNA, 核糖体RNA)messenger RNA (mRNA, 信使RNA)transfer RNA (tRNA, 转运RNA)3Section 2 Chemical Composition. Hydrolysis of nucleic acidsnucleic acidsnucleotidesphosphoric acidnucleosidesnucleosidespentaosepurine bases and pyrimidine basesDNA: H3PO4, deoxyribose, A, G, C, TRNA: H3PO4, ribose, A, G, C, U4Sugars in DNA and RNARNA is derived from riboseDNA is from 2-deoxyriboseu(the is used to refer to positions on the sugar portion of a nucleotide)b-D-riboseb-D-deoxyribose5Heterocycles in DNA and RNAAdenine, guanine, cytosine and thymine are in DNARNA contains uracil rather than thymineAdenine DNA, RNAGuanine DNA, RNACytosine DNA, RNAThymine DNAUracil RNA6. Chemical Composition of Nucleic AcidsElements of nucleic acids:C, H, O, N, P, etc.The amount of P in different nucleic acids are similar, about 910% (w/w). 7adenosine(1) RNA:guanosine1. Nucleosides 核苷核苷In DNA and RNA the heterocycle is bonded to C1 of the sugar.8cytidineuridine9(2) DNA:deoxyadenosinedeoxyguanosinedeoxycytidinedeoxythymidine102. Nucleotides 核苷酸核苷酸A phosphorylated nucleoside, the phosphate is bonded to C5 (and connected to 3 of the next unit). One of the monomers of which DNA and RNA are composed. nucleotides of DNAnucleotides of RNA11OHOCH2SugarHHHA Nucleotide: Adenosine Mono Phosphate (AMP)OHNH2NNNNBasePOOHHOOPhosphate23451NucleotideNucleosideH+-12Section 3 Structure of Nucleic AcidsNucleotides join together in DNA and RNA by as phosphate between the 5-on one nucleotide and the 3 on another One end of the nucleic acid polymer has a free hydroxyl at C3 (the 3 end), and the other end has a phosphate at C5 (the 5 end).13OHOHOHThese bases can be different in RNA and DNAThis OH at the 2-position is present in RNA, but absent in DNA 14NA are linear polymers of nucleotides3-5 phosphodiester bridges link nucleotides together to form nuleic acids1516Nucleic Acid SequencesDifferences arise from the sequence of bases on the individual nucleotides.17Describing a SequenceChain is described from 5 end, identifying the bases in order of occurrence, using the abbreviations A for adenosine, G for guanosine, C for cytidine, and T for thymidine (or U for uridine in RNA) A typical sequence is written as TAGGCT18The sequence of bases along the pentose-phosphodiester backbone of a DNA molecule (or an RNA molecule) read from the 5 end to the 3 end. Primary structure19. Higher ordered structureThe amounts of the bases adenine (A) and thymine (T) (in DNA), adenine (A) and uridine (U) (in RNA), guanidine (G) and cytosine (C) ( in both DNA and RNA) were always equal. We call them base pairs.20Guanine And CytosineNOHNONNHCytosineHONNNNNHHGuanine-+-21Adenine And ThymineCH3NONONH+-ThymineNNNNHNH-+Adenine22ATGC23NOHNONNHCytosine-+-NNNNHNH-+AdenineAdenine And Cytosine24CH3NONONH+-ThymineHONNNNNHHGuanine+-Guanine And Thymine25SUGAR-PHOSPHATE BACKBONEHPOHOOOCH2HOHPOOHOOOCH2HPOOHHOOOCH2NH2NNNNOONH2NNHNNNONH2NB A S E SDNAOHPOHOOOCH2HOOH2NNHNNNHHPOHOOCH2OONOH2NNHH2OHOHPOOHOOCH2CH3OOHNNH2O26In 1953 James D. Wattson and Francis H. C. Crick discovered that the structure of DNA was that of a double-stranded helix in which the two DNA chains were held together in the helix by A-T and G-C hydrogen-bonded base pairs. The diameter of the helix is about 2 nm, and there are 10 residues per turn of helix. Each turn is about 3.4 nm long.Secondary structure of DNA27This shape is now iconic. When you see an image check whether it undergoes a complete turn every 10 bases!10 base pairsWatson J & Crick F (1953). Molecular structure of the nucleic acids: A structure for deoxynucleic acids. Nature 171 p. 737-73828GroovesThe strands of the DNA double helix create two continuous grooves (major and minor) The sugarphosphate backbone runs along the outside of the helix, and the amine bases hydrogen bond to one another on the insideThe major groove is slightly deeper than the minor groove, and both are lined by potential hydrogen bond donors and acceptors.大沟小沟293031Francis CrickJune 8, 1916-July 28, 2004James Watson April 6, 1928-32Maurice Wilkins 15 December 1916 - 5 October 200433The critical X ray image of DNARosalind Franklin (1920-1958)(who died of cancer before the Nobel prize was awarded)This X shape was enough to show Watson that the molecule must be a double helix, whose spacing he could deduce.34James D.WatsonThe DOUBLE HELIXA Personal Account of the Discovery of the Structure of DNA 双螺旋双螺旋发现DNA结构的故事JD沃森 著353637In an interview published Sunday in The Times of London (October 14, 2007), Dr. Watson is quoted as saying that while “there are many people of color who are very talented,” he is “inherently gloomy about the prospect of Africa.” “All our social policies are based on the fact that their intelligence is the same as ours whereas all the testing says not really,” the newspaper quoted him as saying.Watson, who arrived in Britain on Thursday to promote his new book, Avoid Boring People: Lessons From a Life in Science, Hunt-Grubbe stated that Watsons hope was everyone is equal but quoted him as having said people who have to deal with black employees find this not true. 38Three types of duplex A- form, clockwise or right-handed duplex, squat with no major or minor groves. A minor form of duplex, found in RNA and DNA hybrid molecules. B- form, clockwise or right-handed duplex, with major and minor groves. The major form of DNA. Z- form, anti-clockwise or left-handed duplex, which zigs and zags, found in regions which affect gene expression39A-formZ-formB-formMajorMajorMajorMinorMinorClockwiseClockwiseAnti-clockwiseRight-handedRight-handedLeft-handed404142Q. If a DNA duplex is right-handed what does this mean?A. If you stand bottom of the duplex and look up through the duplex it moves away from you in a clockwise direction.43北大后湖附近一个左手性的DNA双螺旋雕塑 4445Duplex DNA structures are stable because: 1.Hydrophobic bases are in the centre of the duplex, furthest away from water, and stabilised by hydrogen bonding between bases.2.Hydrophilic phosphate in the sugar-phosphate backbone is in contact with water and stabilised by electrostatic interactions with water.3.Stacked bases have weak electrostatic interaction van der Waals forces.46Single-stranded RNA molecules adopt secondary structures through base-pairing for similar reasons.47Denaturation (变性): Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. Renaturation (复性 ): The reassociation of denatured complementary single strands of a DNA double helix.Annealing (退火): Spontaneous alignment of two complementary single polynucleotide (RNA, or DNA, or RNA and DNA) strands to form a double helix.48TACTCGACATGCTAGCACATGAGCTGTACGATCGTGDouble stranded DNATACTCGACATGCTAGCACATGAGCTGTACGATCGTGDouble stranded DNARenaturationTACTCGACATGCTAGCACATGAGCTGTACGATCGTGDenatured DNADenaturationSingle stranded DNA49505152HPO-OOOCH2HOHPOO-OOOCH2HPOO-OOOCH2NH2NNNNOONH2NNHNNNONH2NOHPOOOCH2OH2NNHNNNHPO-OOCH2OONOH2NNHOHPOO-OOCH2CH3OOHNNO-O-Distribution of Negative Charge Prevents DNA Annealing53NaClOHPOOOCH2OH2NNHNNNHPO-OOCH2OONOH2NNHOHPOO-OOCH2CH3OOHNNO-O-NaClCl-Na+Cations can cancel out the negative charge carried on the sugar phosphate backbone.HPO-OOOCH2HOHPOO-OOOCH2HPOO-OOOCH2NH2NNNNOONH2NNHNNNONH2NSalts Allow DNA Annealing54HPO-OOOCH2HOHPOO-OOOCH2HPOO-OOOCH2NH2NNNNOONH2NNHNNNONH2NNa+Na+Na+Na+Na+Na+Na+OHPOOOCH2OH2NNHNNNHPO-OOCH2OONOH2NNHOHPOO-OOCH2CH3OOHNNO-O-Na+Na+55HPO-OOOCH2HOHPOO-OOOCH2HPOO-OOOCH2NH2NNNNOONH2NNHNNNONH2NNa+Na+Na+Na+Na+Na+Na+Na+OHPOOOCH2OH2NNHNNNHPO-OOCH2OONOH2NNHOHPOO-OOCH2CH3OOHNNO-O-56ATP is the Universal Energy SourceATP, Adenosine Triphosphate, 三磷酸腺苷57Photosynthesizers get energy from the sun.Animals get energy second- or third-hand from plants or other organisms. They break down carbohydrates, fats, and proteins.58AMPADPATPhigh-energy phosphoryl bond (7.3 kcal/mol or 30.52 kJ/mol) Energy4.3 kcal/mol or 18 kJ/mol59Before cells can use the energy of sunlight or energy /calories stored in carbohydrates, they must transfer the energy to molecules of ATP.ATP is composed of adenine, ribose, and three phosphate groups.ATP transfers energy to many different chemical reactions; almost all metabolic pathways directly or indirectly run on energy supplied by ATP. 60化能有机营养化能无机营养光能营养61Fluorouracil, 5-FU, 5-氟尿嘧啶氟尿嘧啶5-FU is a typical antineoplastic agent.Agents interfering with DNA synthesis(Antimetabolite antitumor agents)62Cytarabine, 阿糖胞苷63Mercaptopurine, 巯嘌呤64Antiviral agentsAciclovir, 阿昔洛韦65Anti HIV AgentsNucleoside reverse transcriptase inhibitorsAzidothymidine, AZT, Zidovudine, ZDV, 叠氮胸苷叠氮胸苷, 齐多夫定齐多夫定AZT is the first approved agent by FDA to treat AIDS.66Dideoxycytidine, DCC, 双脱氧胞苷双脱氧胞苷Dideoxyinosine, DCI, 双脱氧肌苷双脱氧肌苷67Flavour enhancer (Salted delicious, 鲜味剂)Disodium Guanosine-5-monophosphateGMP, 鸟苷酸二钠 Disodium Inosine-5-Monophosphate IMP, 肌苷酸二钠