Biopolymers IV
Polynucleotides
Introduction
Polynucleotides, which are more often called nucleic acids, are polymeric glycosylamines in which the polymer backbone consists of sugars that are linked together by phosphodiester bonds. There are two types of nucleic acids, those in which the polymer backbone is composed of D-ribose units and those in which it is composed of D-2-deoxyribose units. Nucleic acids based on these two sugars are called ribonucleic acids (RNA) and deoxyribonucleic acids (DNA), respectively. Figure 1 identifies the essential structural features of the repeat unit of RNA.
Figure 1
The Repeat Unit of RNA
The D-ribose portion of the structure is shown in red. The blue B represents any of the four heterocyclic bases shown in Figure 2. The phospho diester group that links C3 of one D-ribose unit with C5 of the next is shown in green. The term nucleic acid reflects the fact that phosphoric acid, H3PO4, is a tribasic acid, i.e. it has three acidic OH groups. Two of them are involved in the formation of the phosphodiester bonds that link one sugar to the next. The third is available to act as an acid.
Figure 2
The Heterocyclic Bases in RNA
One of these four heterocyclic bases is attached to the anomeric carbon of each D-ribose unit in the polymer chain. Adenine and guanine are members of a class of heterocyclic bases called purines. Cytosine and uracil belong to the family called pyrimidines.
Exercise 1 Draw the structure of the two dinucleotides that contain adenine and cytosine.
In DNA, the sugar is D-2-deoxyribose. Instead of having uracil as one of the four heterocyclic bases attached to each anomeric carbon of the sugar, DNA has thymine. Figure 3 presents the structure of D-2-deoxyribose and thymine for comparison to Figures 1 and 2.
Figure 3
The Structures of D-2-Deoxyribose and Thymine
Keto-Enol Tautomerization
Each of the 5 heterocyclic bases mentioned above contains an aromatic system of pi electrons, although it is not obvious in guanine, cytosine, uracil, and thymine because these bases exist as keto tautomers. Figure 4 shows the two tautomeric forms of thymine.
Figure 4
Tautomerization in Heterocyclic Bases
The aromatic six pi electron system is more obvious in the enol tautomer of thymine.
Exercise 2 Using water as both an acid and a base, write equations to show how the protons are transferred from the nitrogens to the oxygen atoms in thymine.
Exercise 3 Ultraviolet radiation is known to damage DNA. One UV-induced reaction that has been implicated in such damage involves a 2+2 cycloaddition of a thymine molecule on one sugar with a second thymine on an adjacent sugar. The formation of this "cyclobutylthymine dimer" is thought to cause a local distortion of the shape of the DNA, thereby altering its activity. Draw the structure of the dimer that is formed by the 2+2 cycloaddition of the keto forms of two thymine molecules.
The Primary Structure of Nucleic Acids
The primary structure of nucleic acids describes the sequence of heterocyclic bases attached to the anomeric carbon of each sugar in the polymer backbone. A compact description of the primary sequence is afforded by using the 1-letter abbreviation of each of the heterocyclic bases. For example, AAGCUC describes an oligoribonucleotide in which the heterocylcic bases are adenine, adenine, guanine, cytosine, uracil, and cytosine. Figure 5 shows the structure of the compound.
Figure 5
The Structure of AAGCUC
The 6 letter string is read from the 5' end towards the 3' end of the chain. Note that since uracil occurs in RNA and thymine in DNA, the sequence AAUCGC identifies this nucleic acid chain as a ribonucleic acid.
The Secondary Structure of Nucleic Acids
It is hard to imagine anyone who hasn't heard of the a-helix of DNA. This is the dominant secondary structure of this polynucleotide. But the a-helix of DNA is, in fact, a double helix, i.e. one strand of DNA is wrapped around another. In proteins the association of two polypeptide chains is considered an aspect of quaternary structure, but in nucleic acids, the intertwining of two a-helices is regarded as part of the polymer's secondary structure.
Hydrogen Bonding: Inter-Chain Association
The elucidation of the structure of DNA required the efforts of many people and the interpretation of huge amounts of data. A key part of that data was the observation that the ratio of certain pairs of heterocyclic bases was nearly 1/1 regardless of the source of the DNA. For example, the A/T ratio in DNA obtained from wheat germ was 1.01/1, while that from human liver tissue was 1.00/1. The G/C ratio in DNA from these two species was 1.00/1 and 0.98/1, respectively. These ratios suggested a 1/1 correspondence between adenine bases on one chain of the double helix and thymine bases on the other. Similarly, it seemed reasonable to assume that each cytosine on one chain was associated with a guanine on the other. The "association" assumed was hydrogen bonding. Figure 6 shows idealized representations of the inter-chain H-bonding between A and T and G and C bases.
Figure 6
H-Bonding Between Heterocyclic Bases in DNA
Note that in both cases a purine base is associated with a pyrimidine base. Note, too, that the A/T base pair involves two H-bonding interactions, while the G/C pairing entails three.
If you would like to explore the structures of some DNA molecules, go to Molecules to Explore at USM's Biochemistry web site. There you will find four interactive structures of DNA molecules. For the brave of heart there is also a RasMol tutorial if you are interested in learning how to view all of the structural features of a protein or DNA molecule.
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