nucleic acids

nucleic acids

1. Describe the properties of nucleic acids

   • genetic info mustbe stored in a form that is managable in size and stable over a long period
   • genetic info must be decoded- transcription - nucleotide sequence is copied onto the RNA so that proteins can be translated
   • Info contained in the DNA / RNA must be accessible to proteins ad other nucleic acids
   • DNA is replicated so that the daughter cell receives the same copy

2. Describe the relationship between DNA, RNA and protein

   • DNA sequences are always written as 5'- 3' orientation
   • COLLINEARITY : when amino acids sequences in the polypeptide corresponds to the codon sequences in the nucleaic acid

3. Describe the structure of nucleotides

   • 5 carbon chain sugar PENTOSE
     • deoxyribose - no OH-
     • ribose - OH present
   • phosphate group
     • ARE ATTACHED TO THE 5'CARBON OF THE SUGAR
   • Four nitrogenous bases
     • Purines (2 rings) : adenine & guanine
       • Adenine has an NH2- group
       • guanine has a C=O and NH2- group
       • BOND AT 9 NITROGEN
     • Pyramidines (1 ring) : thymine and cytosine and uracil
       • uracil is very similar to cytosine
         • uracil has =O
         • cytosine has NH2
       • thymine has 2 C=O and CH3 groups
       • BOND AT 1 NITROGEN
     • ARE ATTACHED TO THE 1'CARBON OF THE PENTOSE SUGAR BY A COVALENT BOND

4. Explain giving examples how nucleotide analogues and antifolates function as chemotherapeutic and antiviral agents

   • ANTIMETABOLITES:ANALOGUES OF PURINE AND PYRAMIDINE BASES OR NUCLEOTIDES - ANTITUMOR, ANTIVIRAL AND ANTIMICROBIAL
   • 6- MERCAPTOPURINE INHIBITS THE 1ST STEP OF THE PURINE SYNTHESIS
     • since the cancer cells proliferate at a high rate - they are more sensitive to the inhibitors, as they require a larger number of nucleotides
   • METHOTREXATE INHIBITS THE DIHYDROFOLATE REDUCTASE (HAS X1000 GREATER AFFINITY THAN HF2 - FOLATE ANALOGUE (ACTS AS A COMPETITIVE INHIBITOR
     • Lethal dose of methatraxate is given and then the patient is 'rescued' by giving the 5-formylTHF or thymidine i.e the final product of the whole synthesis
     • if there is not enough dTMP, the DNA starts to utilise the dUMP(which is at a higher concentration but then the DNA is required to repair the DNA by the uracil gycoslase if there is not enough dTTP --> the DNA breaks down
   • 5-FLUROOURACIL INHIBITOR OF DNA SYSNTHESIS - FUra IS A PYRAMIDINE ANALOGUE OF URACIL
     • 5-fluorouracil is converted by normal metabolic enzymes to 5' -fluoro-2-deoxyuridine 5'-monophoasphate (FdUMP)
     • it is an irreversible inhibitor of the thymidylate synthase thus inhibits dTMP production
     • suicide substrates
     • adrucil, efudex, fluracil
   • ACYCLOVIR IS A PURINE ANALOGUE IN THE HERPES VIRUS
     • DNA which contianes hepres encode deoxypyrimidine kinase - which phosphorylates purine analogues into their triphosphate --> thus incorporate into the DNA and prevents further synthesis of the DNA
   • AZT IN AIDS PATIENTS WHICH IS AN ANALOGUE TO THYMIDINE
     • AZT misses the OH- group thus does not allow further growth of the the DNA
     • the aids virus has an RNA genome which uses reverse transcriptase - n this stage AZT is incorporated into growing DNA chain as a thymidine analogue

5. List the structural properties of the Watson and Crick DNA right-handed double helix

   • two polynucleotide chains wound around each other in a right handed double helix
   • antiparallel chains - opposite polarity
   • sugar-phosphate backbones on the outside of the double helix and the the bases are oriented in the inside of the double helix
   • complimentary base pairs
   • 0.34 nm apart in the DNA helix
   • 10 base pairs per turn
   • grooves of unequal size, major and minor grooves

6. Identify the base pairs that form in the DNA

   • GUANINE AND CYTOSINE -> 3 H-BONDS
   • THYMINE/URACIL AND ARGANINE -> 2 H-BONDS

7. Name the type of bonds that hold the base pairs toghether and explain their functional importance

   • nucleotides are linked together by a covalent bond between the phosphate group (5') and the pentose sugar (3') - phosphodiester bonds
   • purine + pyramidine --> H-bonding
   • H-boding is relatively weak (TA - 2 &GC - 3)
   • complimentary base pairing

8. Describe and original experiment that concluded that DNA was the carrier of genetic infromation

   • Friedrich Miesscher white blood cells with HCl to obtain nuclei for study, treated it with acid a precipitate containing C,H,O,N and P --> acidic

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