Nucleic Acids

Structure and properties

Nucleic acids are biomolecules found in all living things on Earth. A distinction is made between ribonucleic acid (RNA, RNA, ribonucleic acid) and deoxyribonucleic acid (DNA, DNA, deoxyribonucleic acid). Nucleic acids are polymers composed of so-called nucleotides. Each nucleotide consists of the following three units:

  • Sugar (carbohydrate, monosaccharide, pentose): ribose in RNA, 2`-deoxyribose in DNA.
  • Inorganic phosphate (phosphoric acid, as ester).
  • Organic nucleic bases: Purine bases: Adenine, guanine; pyrimidine bases: Cytosine, Thymine (in DNA) and Uracil (in RNA).

Via phosphodiester linkage, nucleic acids sometimes form extremely long, linear chains. The backbone is alternately composed of the phosphate and sugar units. The different bases are attached to the sugars. The strands end at the 5′-end (phosphate) and at the 3′-end (hydroxyl group) and therefore have one direction (5′3′ or vice versa). Nucleic acids are synthesized by polymerases such as DNA polymerase (DNA) or RNA polymerase (RNA). The compound of a sugar with a base is called a nucleoside in the absence of the phosphate. A distinction is made between ribonucleosides and deoxyribonucleosides. For example, the base is called adenine, the nucleoside adenosine and the deoxynucleoside deoxyadenosine. Nucleotides or phosphorylated nucleosides have other functions in the organism, for example, as energy carriers (adenosine triphosphate) or for signal transduction (cyclic guanosine monophosphate, cGMP).

Deoxyribonucleic acid (DNA).

Deoxyribonucleic acid (DNA) is usually double-stranded and has a double helical and antiparallel structure. This means that the two strands run in the opposite direction. The following four bases are found in DNA:

  • Purines: adenine (A), guanine (G).
  • Pyrimidines: thymine (T), cytosine (C)

The bases of the two strands form the so-called base pairs via hydrogen bonds. Either between adenine and thymine (A=T) or between guanine and cytosine (G≡C).

Ribonucleic acid (RNA)

Ribonucleic acid (RNA), unlike DNA, is usually single-stranded and it contains uracil (U) instead of thymine. Furthermore, the sugar is ribose instead of the 2`-deoxyribose in DNA. These two sugars differ only in one hydroxy group, which is missing in the 2`-deoxyribose (deoxy = without oxygen). RNA can assume very different structures in space. Different types exist with different tasks:

  • Messenger RNA (mRNA): transcription.
  • Ribosomal RNA (rRNA): Together with proteins, a component of ribosomes.
  • Transfer RNA (tRNA): Protein synthesis.

In viruses, RNA can take over the function of DNA as a carrier of genetic information, for example, in the influenza viruses or hepatitis C viruses. These are referred to as RNA viruses.

Genetic code, transcription, and translation.

Three consecutive bases in each DNA or mRNA (codon) code for an amino acid, the building blocks of proteins. Sections of DNA are first transcribed into mRNA (messenger RNA) during transcription. The formation of proteins from mRNA at the ribosome is called translation.

Function and importance

Nucleic acids have a fundamental importance as information stores. DNA contains the information required for the formation, development, and homeostasis of every living thing. This is primarily the sequence of amino acids in proteins. The sequence tRNA and the rRNA is also “stored” in the DNA. The tasks of ribonucleic acids (RNA) are broader. Like DNA, they are information carriers, but they also have structural and catalytic functions and recognition functions. Nucleic acids reveal that living organisms on earth are related to each other and descend from a common ancestor that existed more than 3.5 billion years ago. Genetics thus provides answers to fundamental questions about life.

Nucleic acids in pharmaceuticals (examples).

Nucleoside analogues such as aciclovir or penciclovir are administered for the treatment of viral infections. They are derivatives of nucleosides that lead to chain termination after phosphorylation and incorporation into viral DNA because the sugar moiety is incomplete. They are false substrates that interfere with DNA replication.Other antiviral drugs also exert their effects at the nucleic acid level. Cytostatics or antimetabolites have a similar function. They are used for cancer therapy. They inhibit cell division and lead to cell death of the cancer cells. Various gene therapeutics are used to modify DNA segments, for example with the CRISPR-Cas9 method. This is done, for example, with the aim of correcting a mutation that causes a disease. In gene therapy, nucleic acids can also be introduced into cells that are not integrated into the genome. They are located outside, but are also used for protein synthesis (e.g. onasemnogen abeparvovec). Small interfering RNA (siRNA) are short RNA fragments that lead to the selective degradation of complementary mRNA in the organism. In this way, they specifically prevent gene expression and the formation of proteins. Furthermore, many drugs interact with nucleic acids and influence gene expression. Typical examples are the glucocorticoids, estrogens, androgens and retinoids. They bind to receptors inside the cell, which subsequently bind to DNA and influence protein synthesis. In addition, nucleic acids play a very important role in diagnosis, drug discovery, and the production of biologics (e.g., insulins, antibodies), among other applications.