Nucleosides and Nucleotides

What are nucleotides?

They are the monomers (building blocks) that make up nucleic acids

What happens when you hydrolyze DNA or RNA?

You get nucleotides

What is hydrolyzing?

It is when you enzymatically degrade a molecule

Describe the composition of nucleotides

1. Sugar

2. Base

3. Phosphate

Describe the composition of a nucleoside

1. Sugar

2. Base

What sugar is used for nucleosides and nucleotides?

It is a Pentose (5 carbon sugar) but more specifically is ribose (can be deoxyribose)

What does deoxyribose mean?

That there is no hydroxyl functional group at the 2’ carbon (instead there is a H)

What does ribose mean?

That there is a hydroxyl functional group at the 2’ carbon

How does the numbering scheme work for nucleotides?

The 1’ carbon starts at where the carbon is glycosidically bonded to the base

Can deoxyribose or ribose undergo more reactions? Why?

Ribose can because it contains the hydroxyl functional group at the 2’ carbon

What bases are purines? How many rings do purines have?

A and G (adenine and guanine). Two rings

What bases are pyrimidines? How many rings do pyrimidines have?

C, T, and U (Cytosine, thymine, uracil). One ring

What functional groups does adenine contain?

Amine

What functional groups does guanine contain?

Amine and ketone

What functional groups does cytosine contain?

Amine and ketone

What functional groups does thymine have?

Amine, ketone, and methyl

What functional groups does uracil have?

Amine and ketone

Is it possible to have phosphates at the 3’ position? If yes why?

Yes because there is a hydroxyl group there

In an RNA molecule, where can a phosphate be attached?

1. At the 2’ location

2. At the 3’ location

3. At the 5’ location

In a DNA molecule, where can a phosphate be attached?

1. At the 3’ location

2. At the 5’ location

What is cAMP? When is it formed?

It is a cyclic adenosine monophosphate that is formed during alkaline hydrolysis or enzymatic cleavage of RNA.

What is cAMP used for?

It is a signalling molecule in many biological processes

How many phosphates can attach to a sugar?

Up to three

How do we name the phosphates?

The phosphate that is bonded to the 5’ carbon is alpha, then beta, and then gamma

What are dideoxy nucleotides?

They are chain terminating nucleotides that lack a 2’ and 3’ hydroxyl group.

Why are dideoxy nucleotides chain terminating?

This is because the lack of a 3’ hydroxyl group. Synthesis cannot occur and thus they can only be added to the chain.

What happens to the charge of the molecule when pH is changed?

The net charge will change because ionizable groups will be in different states of protonation

What is Ka?

It is the dissociation constant of an acid (is the equilibrium constant)

What happens when pH=pKa

50% protonated, 50% deprotonated

What happens when pH is higher than pKa by 1 or more?

100% deprotonated

What is a primary phosphoryl group?

It is the group that loses its proton first

What is the secondary phosphoryl group?

It is the group that loses the second proton

What is the only difference between thymidine and uridine?

A methyl group

What are nucleoside analogues?

They are similar to a specific nucleoside that can be incorporated into growing DNA strands

How do nucleoside analogues act?

1. Chain terminator

2. Inhibit the synthesis of viral or cancer cell DNA

What is didanosine (ddl)?

It is an anti-HIV drug that is a chain terminator

What is cytarabine?

It is an anti-cancer chemotherapy drug

What is lamivudine?

It is a target for viral RTase. It inhibits reverse transcription. It is an analogue to cytidine

Are nucleosides or nucleotides better at getting into the cell?

Nucleosides are better because there are nucleoside transporters that allow them to enter from the blood stream

Why are nucleoside drugs given for cancer?

This is because they are not charged at physiological pH

What are 2 challenges associated with nucleoside analogs in drug therapy?

1. Avoiding harm to normal cells

2. Entering the cell

What are two ways that we can avoid harm to normal cells by using nucleoside analogs?

1. Target viral RTase with specificity

2. Target cancer cells that are hyperactive in DNA replication