Alkylating antineoplastic agentAn alkylating antineoplastic agent is an alkylating agent used in cancer treatment that attaches an alkyl group (CnH2n+1) to DNA. The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the purine ring. Since cancer cells, in general, proliferate faster and with less error-correcting than healthy cells, cancer cells are more sensitive to DNA damage—such as being alkylated. Alkylating agents are used to treat several cancers.
ChemotherapyChemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs) or it may aim to prolong life or to reduce symptoms (palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.
DNADeoxyribonucleic acid (diːˈɒksᵻˌraɪboʊnjuːˌkliːᵻk,_-ˌkleɪ-; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.
DNA polymeraseA DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create two identical DNA duplexes from a single original DNA duplex. During this process, DNA polymerase "reads" the existing DNA strands to create two new strands that match the existing ones. These enzymes catalyze the chemical reaction deoxynucleoside triphosphate + DNAn pyrophosphate + DNAn+1.
Fusion proteinFusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this fusion gene results in a single or multiple polypeptides with functional properties derived from each of the original proteins. Recombinant fusion proteins are created artificially by recombinant DNA technology for use in biological research or therapeutics.
History of cancer chemotherapyThe era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by the early researchers still apply. The beginnings of the modern era of cancer chemotherapy can be traced directly to the German introduction of chemical warfare during World War I. Among the chemical agents used, mustard gas was particularly devastating.
Chemotherapy-induced peripheral neuropathyChemotherapy-induced peripheral neuropathy (CIPN) is a nerve-damaging side effect of antineoplastic agents in the common cancer treatment, chemotherapy. CIPN afflicts between 30% and 40% of patients undergoing chemotherapy. Antineoplastic agents in chemotherapy are designed to eliminate rapidly dividing cancer cells, but they can also damage healthy structures, including the peripheral nervous system. CIPN involves various symptoms such as tingling, pain, and numbness in the hands and feet.
Amino acidAmino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the α-amino acids, from which proteins are composed. Only 22 α-amino acids appear in the genetic code of all life. Amino acids can be classified according to the locations of the core structural functional groups, as alpha- (α-), beta- (β-), gamma- (γ-) or delta- (δ-) amino acids; other categories relate to polarity, ionization, and side chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or sulfur, etc.
Protein targetingProtein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, the plasma membrane, or to the exterior of the cell via secretion. Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell; errors or dysfunction in sorting have been linked to multiple diseases.
AlkylationAlkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting alkylation. Alkyl groups can also be removed in a process known as dealkylation. Alkylating agents are often classified according to their nucleophilic or electrophilic character. In oil refining contexts, alkylation refers to a particular alkylation of isobutane with olefins.
Nitrogen mustardNitrogen mustards are cytotoxic organic compounds with the chloroethylamine ((ClCH2)2NR2) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of cancer. Nitrogen mustards are nonspecific DNA alkylating agents. Nitrogen mustards are not related to the mustard plant or its pungent essence, allyl isothiocyanate; the name comes from the pungent smell of chemical weapons preparations.
DNA repairDNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes.
Okazaki fragmentsOkazaki fragments are short sequences of DNA nucleotides (approximately 150 to 200 base pairs long in eukaryotes) which are synthesized discontinuously and later linked together by the enzyme DNA ligase to create the lagging strand during DNA replication. They were discovered in the 1960s by the Japanese molecular biologists Reiji and Tsuneko Okazaki, along with the help of some of their colleagues. During DNA replication, the double helix is unwound and the complementary strands are separated by the enzyme DNA helicase, creating what is known as the DNA replication fork.
Fragment crystallizable regionThe fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This region allows antibodies to activate the immune system, for example, through binding to Fc receptors. In IgG, IgA and IgD antibody isotypes, the Fc region is composed of two identical protein fragments, derived from the second and third constant domains of the antibody's two heavy chains; IgM and IgE Fc regions contain three heavy chain constant domains (CH domains 2–4) in each polypeptide chain.
DNA profilingDNA profiling (also called DNA fingerprinting and genetic fingerprinting) is the process of determining an individual's deoxyribonucleic acid (DNA) characteristics. DNA analysis intended to identify a species, rather than an individual, is called DNA barcoding. DNA profiling is a forensic technique in criminal investigations, comparing criminal suspects' profiles to DNA evidence so as to assess the likelihood of their involvement in the crime. It is also used in paternity testing, to establish immigration eligibility, and in genealogical and medical research.
Protein engineeringProtein engineering is the process of developing useful or valuable proteins through the design and production of unnatural polypeptides, often by altering amino acid sequences found in nature. It is a young discipline, with much research taking place into the understanding of protein folding and recognition for protein design principles. It has been used to improve the function of many enzymes for industrial catalysis. It is also a product and services market, with an estimated value of $168 billion by 2017.
Fragment antigen-bindingThe fragment antigen-binding region (Fab region) is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. The variable domain contains the paratope (the antigen-binding site), comprising a set of complementarity-determining regions, at the amino terminal end of the monomer. Each arm of the Y thus binds an epitope on the antigen. In an experimental setting, Fc and Fab fragments can be generated in the laboratory.
DNA polymerase betaDNA polymerase beta, also known as POLB, is an enzyme present in eukaryotes. In humans, it is encoded by the POLB gene. In eukaryotic cells, DNA polymerase beta (POLB) performs base excision repair (BER) required for DNA maintenance, replication, recombination, and drug resistance. The mitochondrial DNA of mammalian cells is constantly under attack from oxygen radicals released during ATP production. Mammalian cell mitochondria contain an efficient base excision repair system employing POLB that removes some frequent oxidative DNA damages.
Side chainIn organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a larger hydrocarbon backbone. It is one factor in determining a molecule's properties and reactivity. A side chain is also known as a pendant chain, but a pendant group (side group) has a different definition.
Recombinant DNARecombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be found in the genome. Recombinant DNA is the general name for a piece of DNA that has been created by combining two or more fragments from different sources. Recombinant DNA is possible because DNA molecules from all organisms share the same chemical structure, differing only in the nucleotide sequence.
