Intercalation is the intercalation of particles such as molecules or ions into certain chemical compounds such as crystal lattices. In biochemistry, the term is associated with the intercalation of particles between adjacent base pairs of DNA, which can result in lattice mutations. Intercalary properties are possessed, for example, by the substance thalidomide, which has spawned a malformation scandal.
What is intercalation?
Intercalation is the incorporation of particles such as molecules or ions into certain chemical compounds such as crystal lattices. In chemistry, intercalation is the intercalation of molecules, ions or atoms into chemical compounds. The structure of the particles remains essentially constant during the intercalation process. In inorganic chemistry, intercalation refers primarily to the intercalation of particles between the crystal lattice planes of layered crystals. In this context, for example, the intercalation of an alkali metal in graphite gives rise to new compounds in the form of intercalation complexes. Intercalation compounds of crystals require large interaction forces in the layers involved and minimal ones between adjacent layers. In biochemistry, the term again refers to DNA. In the process, certain molecules insert themselves into the double helix of DNA by sandwiching themselves between pairs of neighboring bases. The process of biochemical intercalation is not a physiological process. It is a pathophysiological process that disrupts DNA replication and transcription. Intercalation is causally associated with genetic mutations that are predominantly relevant in the replication process. Malformations of individual tissues are the result. In addition to mutagenic properties, intercalation in the biochemical sense is also said to have carcinogenic, i.e. cancer-causing, properties. Compounds with intercalative potential include, for example, cytostatics, which are used in cancer therapy. By means of intercalative substances, damage to DNA is induced as part of the treatment, causing the tumor to die.
Function and task
In biochemical intercalation, molecules within DNA insert themselves into the double helix of adjacent base pairs and interfere with the replication and transcription of genetic material. In the replication process, intercalation primarily causes framing mutations, also known as reading frame mutations, reading frame shifts, or frame-shift mutations. Intercalation thus results in the insertion of (3n +1) base pairs, which distorts the grid of the mRNA in the DNA. As a consequence, mutated proteins are formed whose amino acid sequence is altered in all positions from the position of the mutation. Thus, a stop codon is introduced early on, which terminates protein synthesis in terms of translation. Raster mutations towards the end of the reading frame sometimes elongate the polypeptide because they make recognition of the physiological stop codon more difficult. Humans benefit from processes of intercalation primarily through cytostatic drugs used to treat cancer. Despite medical advances in recent decades, cytostatics, due to their intercalative properties, are still considered to be sometimes the most effective treatment for malignant cancer. The toxic chemical substances are used in chemotherapy and disrupt, delay or prevent the cell cycle of the tumor cells, so that the malignant cells no longer spread or disperse. The DNA damage caused by intercalation results in chromosomal aberrations or disrupts the formation of the spindle apparatus. In this way, the division of the target cells is slowed down or switched off. The group of cytostatic drugs includes various substances with chemically very different structures. Well-known intercalative substances of this type are actinomycin, anthracyclines or daunorubicin. Man also benefits from the principle of intercalation in connection with other drugs. For example, the chemotherapeutic effect of antibiotics is also attributed to the intercalation connection.
Diseases and ailments
Thalidomide corresponds to a glutamic acid derivative that has a depressant effect on the central nervous system and shows anti-inflammatory effects in addition to immunosuppressive effects. The substance is considered intercalative.Since thalidomide has sedative, sleep-promoting, anti-inflammatory, anti-tumor growth and blood vessel formation inhibitory effects, it was made available to almost every household as thalidomide at the end of the 1950s. However, due to its intercalative properties, ingestion of the substance during the first three months of pregnancy leads to the intercalation processes described above, which show dramatic effects on embryonic development. The newborns were born with severe malformations of the limbs or internal organs. Due to its intercalative properties, the substance blocks the growth factor VEGF, so that the formation of blood vessels in embryonic development is inhibited. Since the embryo is particularly sensitive to damaging influences during the first three months of development, in addition to malformations, abortion may even occur during this period. Apart from such devastating consequences, intercalative substances are associated with a carcinogenic effect. This applies, for example, to certain dyes. These include ethidium bromide or EtBr, which stains nucleic acid in molecular genetics. Ethidium bromide has the molecular formula C21H20BrN3 and intercalates between the two DNA strands, resulting in staining. Since the dye absorbs UV light in wavelengths from 254 to 366 nm and emits orange-red light with wavelengths of 590 nm, it is irreplaceable as a staining agent in molecular genetics. Ethidium bromide stains DNA samples that have previously been separated using an agarose gel. The dye is added directly to the gel. This results in binding of the dye to the DNA, making the DNA visible in a specific way. Since ethidium bromide is potentially carcinogenic, appropriate safety measures must be taken during use to prevent direct contact with mucosa or skin. The same applies to all other intercalative substances with carcinogenic effects.
