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49-641: Protein A/G is a recombinant fusion protein that combines IgG binding domains of both protein A and protein G . Protein A/G contains four Fc binding domains from protein A and two from protein G, yielding a final mass of 50,460 daltons. The binding of protein A/G is less pH-dependent than protein A, but otherwise has the additive properties of protein A and G. Protein A/G binds to all subclasses of human IgG, making it useful for purifying polyclonal or monoclonal IgG antibodies whose subclasses have not been determined. In addition, it binds to IgA , IgE , IgM and (to

98-489: A chromosomal translocation replaces the terminal exons of one gene with intact exons from a second gene. This creates a single gene that can be transcribed , spliced , and translated to produce a functional fusion protein. Many important cancer -promoting oncogenes are fusion genes produced in this way. Examples include: Antibodies are fusion proteins produced by V(D)J recombination . There are also rare examples of naturally occurring polypeptides that appear to be

147-514: A hexa-his peptide (6xHis-tag), which can be isolated using affinity chromatography with nickel or cobalt resins. Di- or multimeric chimeric proteins can be manufactured through genetic engineering by fusion to the original proteins of peptide domains that induce artificial protein di- or multimerization (e.g., streptavidin or leucine zippers ). Fusion proteins can also be manufactured with toxins or antibodies attached to them in order to study disease development. Hydrogenase promoter, P SH ,

196-468: A pharmacist without needing a doctor's prescription, and prescription only medicines , which must be prescribed by a licensed medical professional , usually a physician . In the United Kingdom, behind-the-counter medicines are called pharmacy medicines which can only be sold in registered pharmacies, by or under the supervision of a pharmacist. These medications are designated by the letter P on

245-470: A stimulant , a sedative , a euphoriant and an anesthetic . The roots of the kava plant are used to produce a drink consumed throughout the cultures of the Pacific Ocean. Some shamans from different cultures use entheogens, defined as "generating the divine within," to achieve religious ecstasy . Amazonian shamans use ayahuasca (yagé), a hallucinogenic brew, for this purpose. Mazatec shamans have

294-419: A study drug , is methylphenidate branded commonly as Ritalin and used for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy . At high doses methylphenidate can become highly addictive . Serious addiction can lead to psychosis , anxiety and heart problems, and the use of this drug is related to a rise in suicides, and overdoses. Evidence for use outside of student settings

343-421: A target molecule was developed using mice and hence were initially "mouse" antibodies. As non-human proteins, mouse antibodies tend to evoke an immune reaction if administered to humans. The chimerization process involves engineering the replacement of segments of the antibody molecule that distinguish it from a human antibody. For example, human constant domains can be introduced, thereby eliminating most of

392-451: A different antibody binding profile in terms of the portion of the antibody that is recognized and the species and type of antibodies. Fusion protein#Recombinant fusion proteins Some fusion proteins combine whole peptides and therefore contain all functional domains of the original proteins. However, other fusion proteins, especially those that occur naturally, combine only portions of coding sequences and therefore do not maintain

441-652: A fusion of two clearly defined modules, in which each module displays its characteristic activity or function, independent of the other. Two major examples are: double PP2C chimera in Plasmodium falciparum (the malaria parasite), in which each PP2C module exhibits protein phosphatase 2C enzymatic activity, and the dual-family immunophilins that occur in a number of unicellular organisms (such as protozoan parasites and Flavobacteria ) and contain full-length cyclophilin and FKBP chaperone modules. The evolutionary origin of such chimera remains unclear. Drug A drug

490-778: A lesser extent) IgD . Protein A/G also binds to all subclasses of mouse IgG but does not bind mouse IgA, IgM or serum albumin. This allows Protein A/G to be used for purification and detection of mouse monoclonal IgG antibodies, without interference from IgA, IgM and serum albumin . Mouse monoclonal antibodies commonly have a stronger affinity to the chimeric protein A/G than to either protein A or protein G. Protein A/G also has been used for purification of macaque IgG. In addition to protein A/G, other immunoglobulin-binding bacterial proteins such as protein A , protein G and protein L are all commonly used to purify, immobilize or detect immunoglobulins . Each of these immunoglobulin-binding proteins has

539-414: A living organism, produces a biological effect. A pharmaceutical drug , also called a medication or medicine, is a chemical substance used to treat , cure, prevent , or diagnose a disease or to promote well-being . Traditionally drugs were obtained through extraction from medicinal plants , but more recently also by organic synthesis . Pharmaceutical drugs may be used for a limited duration, or on

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588-500: A long and continuous tradition of religious use of Salvia divinorum , a psychoactive plant. Its use is to facilitate visionary states of consciousness during spiritual healing sessions. Silene undulata is regarded by the Xhosa people as a sacred plant and used as an entheogen. Its roots are traditionally used to induce vivid (and according to the Xhosa, prophetic) lucid dreams during

637-632: A particular mutation in the EGFR gene. Some drugs are specifically approved for certain genotypes. Vemurafenib is such a case which is used for melanoma patients who carry a mutation in BRAF gene. The number of people who benefit from a drug determines if drug trials are worth carrying out, given that phase III trials may cost between $ 100 million and $ 700 million per drug. This is the motivation behind personalized medicine , that is, to develop drugs that are adapted to individual patients. A medication or medicine

686-449: A regular basis for chronic disorders . Pharmaceutical drugs are often classified into drug classes —groups of related drugs that have similar chemical structures , the same mechanism of action (binding to the same biological target ), a related mode of action , and that are used to treat the same disease. The Anatomical Therapeutic Chemical Classification System (ATC), the most widely used drug classification system, assigns drugs

735-675: A unique ATC code , which is an alphanumeric code that assigns it to specific drug classes within the ATC system. Another major classification system is the Biopharmaceutics Classification System . This groups drugs according to their solubility and permeability or absorption properties. Some religions, particularly ethnic religions , are based completely on the use of certain drugs, known as entheogens , which are mostly hallucinogens ,— psychedelics , dissociatives , or deliriants . Some entheogens include kava which can act as

784-728: A unique ATC code, which is an alphanumeric code that assigns it to specific drug classes within the ATC system. Another major classification system is the Biopharmaceutics Classification System . This classifies drugs according to their solubility and permeability or absorption properties. Psychoactive drugs are substances that affect the function of the central nervous system , altering perception , mood or consciousness . These drugs are divided into different groups like: stimulants , depressants , antidepressants , anxiolytics , antipsychotics , and hallucinogens . These psychoactive drugs have been proven useful in treating wide range of medical conditions including mental disorders around

833-487: Is a drug taken to cure or ameliorate any symptoms of an illness or medical condition. The use may also be as preventive medicine that has future benefits but does not treat any existing or pre-existing diseases or symptoms. Dispensing of medication is often regulated by governments into three categories— over-the-counter medications, which are available in pharmacies and supermarkets without special restrictions; behind-the-counter medicines, which are dispensed by

882-448: Is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via inhalation , injection , smoking , ingestion , absorption via a patch on the skin, suppository , or dissolution under the tongue . In pharmacology , a drug is a chemical substance, typically of known structure, which, when administered to

931-443: Is indicated using -zu- such as in dacli- zu -mab . See the list of monoclonal antibodies for more examples. In addition to chimeric and humanized antibodies, there are other pharmaceutical purposes for the creation of chimeric constructs. Etanercept , for example, is a TNFα blocker created through the combination of a tumor necrosis factor receptor (TNFR) with the immunoglobulin G 1 Fc segment . TNFR provides specificity for

980-582: Is limited but suggests that it is commonplace. Intravenous use of methylphenidate can lead to emphysematous damage to the lungs, known as Ritalin lung . Other drugs known as designer drugs are produced. An early example of what today would be labelled a 'designer drug' was LSD , which was synthesised from ergot . Other examples include analogs of performance-enhancing drugs such as designer steroids taken to improve physical capabilities; these are sometimes used (legally or not) for this purpose, often by professional athletes. Other designer drugs mimic

1029-461: Is still used frequently in modern research. More recent derivations include photoconvertible fluorescent proteins (PCFPs), which were first isolated from Anthozoa . The most commonly used PCFP is the Kaede fluorescent tag, but the development of Kikume green-red (KikGR) in 2005 offers a brighter signal and more efficient photoconversion. The advantage of using PCFP fluorescent tags is the ability to track

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1078-508: Is the use of a drug (legal, controlled, or illegal) with the primary intention of altering the state of consciousness through alteration of the central nervous system in order to create positive emotions and feelings. The hallucinogen LSD is a psychoactive drug commonly used as a recreational drug. Ketamine is a drug used for anesthesia , and is also used as a recreational drug, both in powder and liquid form, for its hallucinogenic and dissociative effects . Some national laws prohibit

1127-478: The Single Convention on Narcotic Drugs exist for the purpose of their prohibition . In English, the noun "drug" is thought to originate from Old French " drogue ", possibly deriving from " droge ( vate )" from Middle Dutch meaning "dry (barrels)", referring to medicinal plants preserved as dry matter in barrels. In the 1990s however, Spanish lexicographer Federico Corriente Córdoba documented

1176-466: The plasma membrane to be recycled, marked by a green fluorescent tag, or may be sent to a lysosome for degradation, marked by a red fluorescent tag. The purpose of creating fusion proteins in drug development is to impart properties from each of the "parent" proteins to the resulting chimeric protein. Several chimeric protein drugs are currently available for medical use. Many chimeric protein drugs are monoclonal antibodies whose specificity for

1225-630: The United States . Where it is legislated against, the degree of prohibition also varies. The Food and Drug Administration (FDA) in the United States is a federal agency responsible for protecting and promoting public health through the regulation and supervision of food safety , tobacco products , dietary supplements , prescription and over-the-counter medications , vaccines , biopharmaceuticals , blood transfusions , medical devices , electromagnetic radiation emitting devices, cosmetics , animal foods and veterinary drugs . In India,

1274-408: The cDNA sequence of the second protein in frame through ligation or overlap extension PCR . That DNA sequence will then be expressed by a cell as a single protein. The protein can be engineered to include the full sequence of both original proteins, or only a portion of either. If the two entities are proteins, often linker (or "spacer") peptides are also added, which make it more likely that

1323-399: The drug target and the antibody Fc segment is believed to add stability and deliverability of the drug. Additional chimeric proteins used for therapeutic applications include: A recombinant fusion protein is a protein created through genetic engineering of a fusion gene. This typically involves removing the stop codon from a cDNA sequence coding for the first protein, then appending

1372-444: The effects of psychoactive drugs. Since the late 1990s there has been the identification of many of these synthesised drugs. In Japan and the United Kingdom this has spurred the addition of many designer drugs into a newer class of controlled substances known as a temporary class drug . Synthetic cannabinoids have been produced for a longer period of time and are used in the designer drug synthetic cannabis . Recreational drug use

1421-579: The following properties: The earliest applications of recombinant protein design can be documented in the use of single peptide tags for purification of proteins in affinity chromatography . Since then, a variety of fusion protein design techniques have been developed for applications as diverse as fluorescent protein tags to recombinant fusion protein drugs. Three commonly used design techniques include tandem fusion, domain insertion, and post-translational conjugation. The proteins of interest are simply connected end-to-end via fusion of N or C termini between

1470-406: The functionality of the protein domains of interest. This technique involves the fusion of consecutive protein domains by encoding desired structures into a single polypeptide chain, but sometimes may require insertion of a domain within another domain. This technique is typically regarding as more difficult to carry out than tandem fusion, due to difficulty finding an appropriate ligation site in

1519-765: The gene of interest. This technique fuses protein domains following ribosomal translation of the proteins of interest, in contrast to genetic fusion prior to translation used in other recombinant technologies. Protein linkers aid fusion protein design by providing appropriate spacing between domains, supporting correct protein folding in the case that N or C termini interactions are crucial to folding. Commonly, protein linkers permit important domain interactions, reinforce stability, and reduce steric hindrance, making them preferred for use in fusion protein design even when N and C termini can be fused. Three major types of linkers are flexible, rigid, and in vivo cleavable. Naturally occurring fusion genes are most commonly created when

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1568-438: The initiation process of shamans , classifying it a naturally occurring oneirogen similar to the more well-known dream herb Calea ternifolia . Peyote , a small spineless cactus , has been a major source of psychedelic mescaline and has probably been used by Native Americans for at least five thousand years. Most mescaline is now obtained from a few species of columnar cacti in particular from San Pedro and not from

1617-424: The interaction of overlapping biochemical pathways in real time. The tag will change color from green to red once the protein reaches a point of interest in the pathway, and the alternate colored protein can be monitored through the duration of pathway. This technique is especially useful when studying G-protein coupled receptor (GPCR) recycling pathways. The fates of recycled G-protein receptors may either be sent to

1666-410: The label. The range of medicines available without a prescription varies from country to country. Medications are typically produced by pharmaceutical companies and are often patented to give the developer exclusive rights to produce them. Those that are not patented (or with expired patents) are called generic drugs since they can be produced by other companies without restrictions or licenses from

1715-401: The original functions of the parental genes that formed them. Many whole gene fusions are fully functional and can still act to replace the original peptides. Some, however, experience interactions between the two proteins that can modify their functions. Beyond these effects, some gene fusions may cause regulatory changes that alter when and where these genes act. For partial gene fusions ,

1764-402: The patent holder. Pharmaceutical drugs are usually categorised into drug classes . A group of drugs will share a similar chemical structure , or have the same mechanism of action , the same related mode of action or target the same illness or related illnesses. The Anatomical Therapeutic Chemical Classification System (ATC), the most widely used drug classification system, assigns drugs

1813-459: The possible origin of the word in {ḥṭr} an early romanized form of Al-Andalus language from Northwestern part of the Iberian peninsula . The term could approximately be transcribed as حطروكة or hatruka . The term "drug" has become a skunked term with negative connotation, being used as a synonym for illegal substances like cocaine or heroin or for drugs used recreationally . In other contexts

1862-426: The potentially immunogenic portions of the drug without altering its specificity for the intended therapeutic target. Antibody nomenclature indicates this type of modification by inserting -xi- into the non-proprietary name (e.g., abci- xi -mab ). If parts of the variable domains are also replaced by human portions, humanized antibodies are obtained. Although not conceptually distinct from chimeras, this type

1911-425: The proteins fold independently and behave as expected. Especially in the case where the linkers enable protein purification , linkers in protein or peptide fusions are sometimes engineered with cleavage sites for proteases or chemical agents that enable the liberation of the two separate proteins. This technique is often used for identification and purification of proteins, by fusing a GST protein , FLAG peptide , or

1960-406: The proteins. This provides a flexible bridge structure allowing enough space between fusion partners to ensure proper folding . However, the N or C termini of the peptide are often crucial components in obtaining the desired folding pattern for the recombinant protein, making simple end-to-end conjoining of domains ineffective in this case. For this reason, a protein linker is often needed to maintain

2009-456: The proviso that it can only be used for personal use. It can be used in the leaf form of marijuana (grass) , or in the resin form of hashish . Marijuana is a more mild form of cannabis than hashish. There may be an age restriction on the consumption and purchase of legal recreational drugs. Some recreational drugs that are legal and accepted in many places include alcohol , tobacco , betel nut , and caffeine products, and in some areas of

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2058-677: The route of administration Numerous governmental offices in many countries deal with the control and supervision of drug manufacture and use, and the implementation of various drug laws. The Single Convention on Narcotic Drugs is an international treaty brought about in 1961 to prohibit the use of narcotics save for those used in medical research and treatment. In 1971, a second treaty the Convention on Psychotropic Substances had to be introduced to deal with newer recreational psychoactive and psychedelic drugs. The legal status of Salvia divinorum varies in many countries and even in states within

2107-424: The shuffling of different active sites and binding domains have the potential to result in new proteins with novel functions. The fusion of fluorescent tags to proteins in a host cell is a widely popular technique used in experimental cell and biology research in order to track protein interactions in real time. The first fluorescent tag, green fluorescent protein (GFP), was isolated from Aequorea victoria and

2156-464: The terms "drug" and "medicine" are used interchangeably. Drug action is highly specific and their effects may only be detected in certain individuals. For instance, the 10 highest-grossing drugs in the US may help only 4-25% of people. Often, the activity of a drug depends on the genotype of a patient. For example, Erbitux ( cetuximab ) increases the survival rate of colorectal cancer patients if they carry

2205-435: The use of different recreational drugs; medicinal drugs that have the potential for recreational use are often heavily regulated. However, there are many recreational drugs that are legal in many jurisdictions and widely culturally accepted. Cannabis is the most commonly consumed controlled recreational drug in the world (as of 2012). Its use in many countries is illegal but is legally used in several countries usually with

2254-601: The vulnerable peyote. The entheogenic use of cannabis has also been widely practised for centuries. Rastafari use marijuana (ganja) as a sacrament in their religious ceremonies . Psychedelic mushrooms ( psilocybin mushrooms ), commonly called magic mushrooms or shrooms have also long been used as entheogens. Nootropics , also commonly referred to as "smart drugs", are drugs that are claimed to improve human cognitive abilities . Nootropics are used to improve memory, concentration, thought, mood, and learning. An increasingly used nootropic among students, also known as

2303-467: The world the legal use of drugs such as khat is common. There are a number of legal intoxicants commonly called legal highs that are used recreationally. The most widely used of these is alcohol. All drugs have a route of administration , and many can be administered by more than one. A bolus is the administration of a medication, drug or other compound that is given to raise its concentration in blood rapdily to an effective level, regardless of

2352-479: The world. The most widely used drugs in the world include caffeine , nicotine and alcohol , which are also considered recreational drugs , since they are used for pleasure rather than medicinal purposes. All drugs can have potential side effects . Abuse of several psychoactive drugs can cause addiction and/or physical dependence . Excessive use of stimulants can promote stimulant psychosis . Many recreational drugs are illicit ; international treaties such as

2401-475: Was studied constructing a P SH promoter- gfp fusion by using green fluorescent protein ( gfp) reporter gene . Novel recombinant technologies have made it possible to improve fusion protein design for use in fields as diverse as biodetection, paper and food industries, and biopharmaceuticals. Recent improvements have involved the fusion of single peptides or protein fragments to regions of existing proteins, such as N and C termini , and are known to increase

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