Chapter 22 Nucleic Acids: Structure & Formation

Nitrogen-Containing Heterocyclic Bases of Nucleotides

- They are bases because they contain amine functional groups which exhibit basic behavior - *Three Pyrimidine Derivatives:* Thymine (T), Cytosine (C), and Uricil (U). - *Two Purine Derivatives:* Adenine (A), Guanine (G).

DNA Double Helix

- Two polynucleotide strands coiled around each other in a manner like a spiral staircase. - The sugar-phosphate backbones of the two polynucleotide strands can be thought of as being the outside banisters of the spiral staircase. - The bases (side chains) of each backbone extend inward toward the bases of the other strand. - The two strands are connected by hydrogen bonds between their bases. - The two strands of the double helix are antiparallel, i.e they run in opposite directions. One strand runs in the 5' —> 3' direction, and the other is oriented in the 3' —> 5' direction.

Nucleotide Formation (Full Reaction)

1. *Nucleoside Formation:* *Condensation Reaction:* Pentose Sugar + Nitrogen Base —> Nucleoside + H20 - The base is always attached to C1′ of the sugar (the anomeric carbon), which is always in a beta-coniguration. The bond connecting the sugar and base is a beta-N-glycosidic linkage. - For purine bases, attachment is through N9. - For pyrimidine bases, N1 is involved. 2. *Nucleotide Formation:* *Condensation Reaction:* Nucleoside + Phosphate Group —> Nucleotide + H20 - The phosphate group is attached to the sugar at the C5′ position through a phosphoester linkage.

What are the two types of Nucleic Acids found within cells?

1. Deoxyribonucleic Acid (DNA) 2. Ribonucleic Acid (RNA)

Characteristics of Primary Nucleic Acid Structure

1. Each nonterminal phosphate group of the sugar-phosphate backbone is bonded to two sugar molecules through a 3′,5′-phosphodiester linkage. A. There is a phosphoester bond to the 5′ carbon of one sugar unit and a phosphoester bond to the 3′ carbon of the other sugar. 2. A nucleotide chain has directionality. A. One end of the nucleotide chain, the 5′ end, normally carries a free phosphate group attached to the 5′ carbon atom. B. The other end of the nucleotide chain, the 3′ end, normally has a free hydroxyl group attached to the 3′ carbon atom. C. By convention, the sequence of bases in a nucleic acid strand is read from the 5′ end to the 3′ end. 3. Each nonterminal phosphate group in the backbone of a nucleic acid carries a 1- (minus one) charge. A. The parent phosphoric acid molecule from which the phosphate was derived originally had three —OH groups. Two of these become involved in the 3′,5′-phosphodiester linkage. The remaining —OH group is free to exhibit acidic behavior—that is, to produce an H+ ion.

What stabilizes the DNA double helix?

1. Hydrogen bonding between base pairs. 2. Base-Stacking interactions.

What are the three parallels between Primary Nucleic Acid structure, and Primary Protein Structure?

1. They have backbones that do not vary in structure. 2. The sequence of attachments to backbones distinguishes them from one another. i.e, R groups in proteins, and nitrogen bases in nucleic acids. 3. They have directionality. i.e. 5' —> 3' in nucleic acids, N-terminal —> C-terminal in proteins.

Draw the Adenine-Thymine Bond

2 H bonds: (A) 6-Amino —— (T) 4-oxo (A) N1 —— (T) N3

Draw the Cytosine-Guanine Bond

3 H bonds: (C) 4-Amino —— (G) 6-Oxo (C) N3 —— (G) N1 (C) 2-Oxo —— (G) 2-Amino

What is the bond that connects the phosphate and pentoses in the primary nucleic acid structure?

3',5'-Phosphodiester Linkage.

Purine

A bicyclist base with fused five and six-membered rings. There are two derivatives of purine that are found in nucleotides: Adenine (A), Guanine (G).

Phosphate

A component of a nucleotide, it is derived from phosphoric acid (H3PO4). Under cellular pH the phosphoric acid loses two of its hydrogen atoms to give a hydrogen phosphate ion (HPO4 ^2-)

Pyrimidine

A monocyclic base with a six-membered ring. There are three Pyrimidine derivatives found in nucleotides: Thymine (T), Cytosine (C) and Uracil (U).

Nucleic Acid Backbone

Alternating sugar-phosphate chain in a Nucleic Acid structure. The backbone is constant throughout the entire Nucleic Acid structure. *For DNA:* Backbone consists of alternating phosphate and deoxyribose sugar units. *For RNA:* Backbone consists of alternating phosphate and ribose sugar units.

Complementary DNA Strands

Are strands of DNA in a double helix with base pairing such that each base is located opposite its complementary base.

What is the bond that connects the sugar and base in a nucleoside?

Beta-N-Glycosidic Linkage.

Complementary Bases (definition, etc.)

Complementary bases are pairs of bases in a nucleic acid structure that hydrogen-bond to each other. *Physical Restrictions:* The size of the interior of DNA double helix limits the base pairs that can H bond to each other. There isn't enough room for two purines to fit, and pyrimidines are too far apart due to their smaller size to H bond with each other. *Hydrogen Bonding:* Adenine-Thymine: Have 2 H bonds Cytosine-Guanine: Have 3 H bonds.

Nucleic Acid Secondary Structure

DNA: Double Helix RNA: Single stranded molecule. RNA can fold back on itself forming double helical regions. If a base sequence along two portions of an RNA strand are complementary, a structure with a hairpin loop results.

How to find the charge of a primary nucleic acid structure

Each phosphate group has a 1- charge in a backbone. A monophosphate has 2- charge, a diphosohate has 3- charge, and a triphosphate has a 3- charge.

DNA Double Helix Hydrogen Bonding Interactions

Hydrogen bonding between base pairs is an important factor in stabilizing the DNA double-helix structure. Although hydrogen bonds are relatively weak forces, each DNA molecule has enough collective base pairs that these hydrogen bonds are a force of signiicant strength.

Deoxyribonucleic Acid (DNA)

Is a nucleotide polymer in which each of the monomers contains deoxyribose, a phosphate group, and one of the heterocyclic bases adenine, cytosine, guanine, or thymine.

Ribonucleic Acid (RNA)

Is a nucleotide polymer in which each of the monomers contains ribose, a phosphate group, and one of the heterocyclic bases adenine, cytosine, guanine, or uracil.

Nucleotide (definition)

Is a three-subunit molecule in which a pentose sugar is bonded to both a phosphate group and a nitrogen-containing heterocyclic base. *Nucleotide = Nucleoside + Phosphate*

Nucleic Acid (definition)

Is an unbranched polymer containing monomer units called nucleotides.

Primary Nucleic Acid Structure

Is the sequence in which nucleotides are linked together in a nucleic acid. - The sugar-phosphate backbone of a given Nucleic Acid does not vary. - The primary structure of the Nucleic Acid depends only on the sequence of bases present.

Are Nucleosides soluble in water? Compared to free heterocyclic bases?

Nucleosides are more soluble in water than free heterocyclic bases because of the hydrophilic nature of the pentose's —OH groups.

Nucleoside Nomenclature

Nucleosides are named as derivatives of the base that they contain; the base's name is modified using a suffix. 1. *Pyrimidine Bases:* the *suffix -idine* is used (cytidine, thymidine, uridine). 2. *Purine Bases:* The *suffix -osine* is used (adenosine, guanosine). 3. *Deoxyribose:* Theprefix deoxy- is used to indicate that the sugar present is deoxyribose (for DNA). 4. *Ribose:* No prefix is used when the sugar present is ribose (for RNA).

Nucleotide Nomenclature

Nucleotides are named by appending the term 5'-monophosphate to the name of the nucleoside from which the are derived. *Ex:* Adenosine 5'-monophosphate *Abbreviations:* - Are used in a manner similar to that for amino acids. - The abbreviations use the one-letter symbols for the base (A, C, G, T, and U), MP for monophosphate, and a lowercase d at the start of the abbreviation when deoxyribose is the sugar

RNA Hairpin Loop

RNA Secondary Structure is a single stranded molecule. RNA can fold back on itself forming double helical regions. If a base sequence along two portions of an RNA strand are complementary, a structure with a hairpin loop results.

Primary Nucleic Acid Structure Notation

Specifying the primary structure for a nucleic acid is done by listing nucleotide base components (using their one-letter abbreviations) in sequential order starting with the base at the 5′ end of the nucleotide strand. It is written 5' —> 3'.

Uracil (U)

The 2,4-dioxo derivative of Pyrimidine. Bonds with Adenine (A), a Purine derivative, only in RNA.

Guanine (G)

The 2-amino-6-oxo Purine derivative. Bonds with Cytosine (C), a Pyrmidine derivative, in DNA and RNA.

Cytosine (C)

The 4-amino-2-oxo derivative of pyrimidine. Bonds with Guanine (G), a Purine derivative in both DNA and RNA.

Thymine (T)

The 5-methyl-2,4-dioxo derivative of Pyrimidine. Bonds with Adenine (A), a Purine, in DNA only.

Adenine (A)

The 6-amino derivative of purine. Bonds to Thymine (T), a Pyrimidine derivative, in DNA and Uracil (U), a Pyrimidine derivative, in RNA.

Pentose Sugars of Nucleotides

The Sugar Unit of a nucleotide. It is either the pentose Ribose in RNA, or the pentose 2'-Deoxyribose. *Structure:* - Ribose: Carbon 2' has an —OH group - Deoxyribose: Carbon 2' has an —H atom.

DNA Double Helix Base-Stacking Interactions

The bases in a DNA double helix are positioned with the planes of their rings parallel (like a stack of coins). Stacking interactions involving a given base and the parallel bases directly above and below it also contribute to the stabilization of the DNA double helix. Purines and Pyrimidines are hydrophobic in nature, so their stacking interaction are associated with hydrophobic molecules, mainly London dispersion forces.

Draw the Adenine-Uracil Bond

Two H bonds: (A) 6-Amino —— (T) 4-Oxo (A) N7 —— (T) N3

Nucleoside (definition)

nucleoside is a two-subunit molecule in which a pentose sugar is bonded to a nitrogen-containing heterocyclic base. *Nucleoside = Sugar + Base*