Biologicals: Peptides, Proteins, Nucleotides, and Macrolides as Drugs

Recombinant proteins are used in replacement therapy, particularly when the body’s own protein is insufficient or malfunctions. Diabetes is caused by a deficiency of the hormone insulin. Today, genetically engineered insulin has also been improved in its properties by mutational changes for either longer or shorter action. Antibodies specifically recognize foreign substances on the basis of their surface properties, efficiently bind to them and deliver them to phagocytic cells, such as macrophages, for degradation. The antigen recognition regions are located at the tips of the antibodies and consist of multiple hypervariable loops that form the complementarity determining regions for binding antigens. This makes them ideal for detecting and eliminating disease-causing foreign substances and malignant or degenerate cells. Antibodies can be raised against surface proteins on tumor cells or to compete with endogenous macromolecular ligands for cell surface receptors. There, they interfere with subsequent steps in signaling cascades. Protein biosynthesis requires the reading of single-stranded mRNA. Hybridization with short sequences of antisense oligonucleotides leads to base pairing, and the resulting double strand is either digested by RNase H or cannot be read during protein biosynthesis. Chemical modifications, either of the phosphate backbone, conformational locking of the ribose moiety, or chemical substitution of functional groups, improve the properties of RNA for successful drug applications. Nucleosides and nucleotides with critical chemical modifications can still be recognized by enzymes as false substrates. They can then be covalently attached to the active site to block a protein or interfere with the polymer chain reaction to stop replication of the viral genome. Delivered in the form of a vaccine, mRNA can provide the blueprint for therapeutically important proteins in the body. Antibodies can be raised against the surface of viral proteins to recognize and eliminate a pathogen. HIV reverse transcriptase can be allosterically blocked by inhibitors that lock the enzyme in an open conformation, preventing recognition of the nascent RNA-DNA hybrid strand. The enzyme gyrase catalyzes the overspiralization of bacterial DNA. The quinolones intercalate into the cut DNA like a wedge and prevent the cleaved ends of the double strands from rejoining in the overspiralization process. Tetracyclines inhibit ribosomal function; however, by binding with high affinity to the Tet repressor, they can induce gene expression of a transport protein that removes foreign substances, including tetracyclines, from a bacterial cell. Macrolides were developed by microorganisms to fight other bacteria and fungi by blocking ribosomal function. The ribosome, acting as a ribozyme, synthesizes the polymer chain of a new protein in the peptidyl transferase center according to the blueprint on the mRNA. Several classes of antibiotics are known to block the ribosome at a few vulnerable points, such as the peptidyl transferase center or the ribosomal peptide tunnel. Resistance to potent ribosomal inhibitors results from nucleoside exchange at sites where the ribosome makes critical interactions with bound inhibitors. https://sn.pub/cizkno