Nucleotide structure, nomenclature, derivatives and analogues

1. Nucleotide Chemistry
BAHS 233

2. Goals
Identify the basic structure of
nucleotides and nucleosides
Identify Nucleotide derivatives and
analogues
Familiar with the different biological
roles of nucleotides

3. Content
Structure of Nucleotides
Naming of Nucleotides
Biomedical Functions of Nucleotides
Nucleotide Derivatives and Functions
Use Nucleotide Analogues as Drugs

4. Nucleoside
Sugar
Base
= Sugar + Base

5. Nucleotide = Nucleoside + Phosphate
Sugar
Base
Phosphate
Nucleoside

6. Composition of Nucleotides
Nucleotide = Nucleoside + Phosphate
Glycosidic Bond is a bond between a sugar and another group
Ester Bond
Glycosidic Bond
Ester Bond is C-O-R and the oxygen is bounded to something
else

7. Composition of Nucleotides
Sugar
Bases
Phosphate

8. • Pentoses (5-C sugars or carbohydrate)
• Numbering of sugars is “primed”
Sugars

9. Ribose : forming Ribonucelotides
Deoxyribose: forming
Deoxynucelotides (d-Nucleotides)
Oxygen missing
Sugars(two types

10. fused five- and six-membered rings
Bases(two types)
Pyrimidines – N 1 forms glycosidic bond with sugar
Purines -N 9 forms glycosidic bond with the sugar
six membered rings

11. Bases( Sub-types)
Adenine A
Guanine G
Thymine T
Uracil U
Cytosine C

12. Pyrimidine Base Structures

13. Purine Base Structures

14. Bases Occurrence
Ribonucleotides only
Ribonucleotides & D-nucleotides
D-nucloetides only

15. • Phosphates can be bonded to either C5 or C3
Phosphate Groups
Ester Bond
•They are linked by an Ester bond

16. Mono, Di, Tri phosphate Groups
Nucleotide 5’-Monophosphate
Nucleotide 5’- Diphosphate
Nucleotide 5’- Triphosphate

17. • Purine nucleosides end in “-sine”
– Ribonucleoside Deoxynucleoside
• Adenosine Deoxyadenosine
• Guanosine Deoxyguanosine
Naming Conventions of Nucleosides
Pyrimidine nucleosides end in “-dine”
– Ribonucleoside Deoxynucleoside
• Deoxythymidine
• Cytidine Deoxycytidine
• Uridine

18. Start with the nucleoside name from above and add
“mono-”, “di-”, or “triphosphate”
Naming Conventions of Nucleotides
Ribonucleotides
Purines
Adenosine monophosphate(AMP), ADP, ATP
Guanosine monophosphate(GMP), GDP, GTP
Pyrimindines
Cytidine Monophosphate, CDP, CTP
Uridine Monophosphate, UDP, UTP

19. Naming Conventions of Nucleotides
Deoxynucleotides
Purines
Deoxyadenosine monophosphate (d-AMP),
d-ADP, d-ATP
d- Guanosine Monophosphate, d-GDP, d-GTP
Pyrimindines
d- Cytidine Monophosphate, d-CDP, d-CTP
d- thymidine Monophosphate, d-TDP, d-TPP

20. Memory Check

21. Memory Check

22. Memory check

23. Phosphodiester Bond (linkages)
Nucleotides are joined together by Phosphodiester bonds
ester bond
ester bond
Phosphodiester bond

24. Voet, Voet & Pratt 2013 Fig 3.3a,b
Nucleic Acids : Polymers of nucleotides
Nucleic acid with deoxy ribose
sugars---Deoxyribonucleic acid
(DNA)
Nucleic acid with Contains ribose
sugar---Ribonucleic acid(RNA)

25. Memory Check

26. Nucleoside Derivatives
Adenosine derivatives
Guanosine derivative
Cytidine derivatives
Uridine derivatives

27. Adenosine Triphosphate (ATP)
3'-5'-Cyclic Adenosine Monophosphate,
“(cAMP or cyclic AMP)
Flavin Adenine Dinucleotide (FAD & FMN)
Nicotinaminde Adenine Dinucleotide
(NAD+ & NADP)
S-adenosylmethionine (SAM)
Common Adenosine Derivatives

28. ATP Structure

29. Adenosine Triphosphate (ATP),
FUNCTIONS
Adenosine Derivatives
1. Energy storage and transfer
2. Release of the third phosphate to produce
adenosine diphosphate, or ADP releases
energy for cell activity

30. Cyclic AMP Structure

31. Cyclic AMP or 3'-5'-cyclic adenosine
monophosphate,
FUNCTIONS
Adenosine Derivatives
1. Second messenger in signal transduction
2.Regulate metabolism e.g. glycogen
breakdown, lipids breakdown etc

32. Flavin Adenine Dinucleotide
(FAD(H2) & FMN(H2) Structure
Flavin
Mononucloetide
(FMN)
Flavin
Coenzyme functioning as
carrier of hydrogen and
electrons in some redox
reactions
sugar
+ H2
Riboflavin
(Vit B 2)
FAD
FMN(H2) or FAD(H2)
phosphate

33. Nicotinamide Adenine Dinucleotide
NAD (H)+ and NADP(H)+ Structures
+ H
Coenzyme functioning
as carrier of hydrogen
and electrons some
redox reactions
NADP
NADPH
NAD

34. Coenzyme A Structure
Coenzyme serving as
acyl group – R(CO) carrier in
certain enzymatic reactions

35. S- adenosylmethionine Structure
Methyl (CH3) donor in methylation reactions

36. Adenosine Triphosphate (ATP)
3'-5'-Cyclic Adenosine Monophosphate,
“(cAMP or cyclic AMP)
Flavin Adenine Dinucleotide (FAD & FMN)
Nicotinaminde Adenine Dinucleotide
(NAD+ & NADP)
S-adenosylmethionine (SAM)
Common Adenosine Derivatives

37. Guanosine Triphosphate (GTP),
FUNCTIONS
Guanosine Derivative
1. Energy store
2.Energy source for Protein synthesis
and Gluconeogenesis
3. Energy source during elongation
stage of translation

38. Thymidine Derivatives
Ribothymindine
Plays a role thermal stability of transfer
RNA

39. Uracil Derivatives
UDP glucoronate ---- glucuronic acid donor
UDP-glucose-,glucose donor in glycogen
synthesis.
UDP-sugar derivatives-----glu, gal, fruc
--- used as sugar donors, used in
glycoproteins and glycolipids synthesis

40. Cytidine Derivatives
CMP-N acetylneuraminic acid (CMP-
NANA) required for the biosynthesis of
glycoproteins
CDP-choline- required for the biosynthesis of
sphingolipids (component of cell membrane of brain and nervious
tissues).
CTP- required for the biosynthesis of
phosphoglycerides (component of cell membrane)
sphingosine

41. Synthetic Analogues of Nucleotides
An analogue is an organic chemical
compound related to another by
substitution of atoms with other groups
Chemically synthesized nucleotides used as
drugs in clinical therapy
Nucleotide analogues are prepared by
altering the base ring or sugar moiety.

42. Synthetic Analogues of Nucleotides:
Anti-tumour agents used in chemotherapy
Interfere with the synthesis of DNA and thereby
preferentially kill rapidly dividing cells such as
tumor cells.
5-fluorouracil
6- mercaptopurine)

43. Synthetic Analogues of Nucleotides:
Anti-tumour agents used in chemotherapy

44. Synthetic Analogues of Nucleotides:
Anti-Viral agents
Used to interfere with the replication of
viruses by terminating DNA synthesis
Lamivudine ----- Hepatitis B
AZT (azidothymidine or zidovudine) - HIV

45. Synthetic Analogues of Nucleotides:
Treatment of Gout
Caused by accumulation of uric acid
Allopurinol is a structural analogue of
hypoxanthine is used treat gout
The drug is an inhibitor of the enzyme xanthine
oxidase which converts hypoxanthine to uric acid

46. Biomedical importance of nucleotides
Precursors of nucleic acids, DNA & RNA
Components of important co-enzymes
( like NAD+ and FAD, Co-enzyme A)
Storage and transfer of energy (ATP and GTP )
Storage and transfer of genetic
information (DNA & RNA)

47. Biomedical importance of nucleotides
Synthetic analogues used in medicine
e.g. 5-fluorouracil
CTP and UTP are both used in the
production of biomolecules
Metabolic rgulators such as cAMP

48. Memory Check

49. Memory Check
Ribonucleotides only
Ribonucleotides & D-nucleotides
D-nucloetides only

50. Adenosine Triphosphate (ATP)
3'-5'-Cyclic Adenosine Monophosphate,
“(cAMP or cyclic AMP)
Flavin Adenine Dinucleotide (FAD & FMN)
Nicotinaminde Adenine Dinucleotide
(NAD+ & NADP)
S-adenosylmethionine (SAM)
Memory Check

51. Memory Check

52. Memory Check

53. Memory Check

54. Memory Check

55. Memory Check

56. Memory Check

57. Memory Check
Guanosine Triphosphate (GTP),
UDP-sugar derivatives; glu, gal, fruc
CMP-N acetylneuraminic acid (NANA)
Cytidine Triphosphate (CTP)

58. Memory Check

59. Content
Structure of Nucleotides
Naming of Nucleotides
Biomedical Functions of Nucleotides
Nucleotide Derivatives and Functions
Use Nucleotide Analogues as Drugs

60. Nucleotide Chemistry
BAHS 233
Thank you

61. Minor Pyrimidine nucleosides

62. Minor Purine Nucleosides