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Lecture 9-04 - Lecture 9/04 Nucleotides DNA and the Central...

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Lecture 9/04 Nucleotides, DNA and the Central Dogma monomers connected by covalent bond to form polymers DNA and RNA monomers also function in catalysis, energy transfer, hormone signal mediation o note that many of the co-substrates have a nucleotide portion--NAD, FAD, etc. purine or pyrimidine ring o nitrogen containing, weak base--hence the term "bases" when referring to the nucleotides o nitrogens can also ionize at different pHs free bases are rarely found in nature--extremely insoluble double bonds absorb UV--used to quantitate nucleotides/nucleic acids Purines --2 rings; G and A found in RNA and DNA Pyrimidines --one ring--C found in RNA and DNA; U in RNA; T in DNA Many other types of purines and pyrimidines are important in tRNAs and as molecules with biological effects (caffeine and theophylline) Nucleosides --contain ribose (RNA-ribonucleosides) or deoxyribose (DNA- deoxyribonucleosides), no phosphate glycosidic bond--C1' carbon of sugar to N-1 of pyrimidines or N9 of purines Nucleoside Derivatives--mimics that lack the ability to be incorporated into DNA--no 3' OH group used to treat AIDS--inhibits replication of HIV virus used to treat Herpes, shingles, chicken pox Nucleotides --OH group of ribose esterified with phosphate monophosphates are dibasic acids with pKa of ~1 and 6 Diphosphates and triphosphates --ATP is given as an example Polynucleotides--DNA, RNA Deoxyribonucleic acids (DNA) backbone of alternating units of 2-deoxy-ribose and phosphate in which the 3 -
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OH of one deoxy-ribose is joined by a phosphodiester bond to the 5 -OH of another deoxy-ribose unit Primary Structure: the sequence of bases along the pentose-phosphodiester backbone of a DNA molecule (or an RNA molecule) 5' end to the 3' end--directionality Secondary structure: the ordered arrangement of nucleic acid strands the double helix model of DNA 2° structure was proposed by James Watson and Francis Crick in 1953 Double helix: 2° structure of DNA molecules in which two antiparallel (5'-->3'/ 3'-->5') or complimentary polynuceotide strands are coiled in a right-handed manner phosphate backbone position minimizes repulsion of negative charges--charges to the outside of the helix Traditional view: stabilizing the double helix is base pairing between T-A and between C-G by hydrogen bonds and base stacking (pi-pi interaction of electrons) "Throughout the temperature and salt concentration range of our experiments, base-stacking interactions are always stabilizing for both A•T- and G•C- containing contacts in the DNA double helix. In fact, DNA stability is mainly determined by base-stacking interactions. G•C pairing does not contribute to stabilization of DNA duplex, while A•T pairing is always destabilizing. This finding presents a paradigm shift in the understanding of the interplay of the forces stabilizing DNA double helix." from Yakovchuk et al (2006) DNA denaturation separate strands of DNA--melting must break H bonds and disrupt base stacking heat or urea
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