Peptide
Encyclopedia
Peptides are short polymer
s of amino acid
monomer
s linked by peptide bond
s. They are distinguished from protein
s on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptide
s, consisting of two amino acids joined by a single peptide bond. There are also tripeptide
s, tetrapeptide
s, etc. Amino acids which have been incorporated into a peptide are termed "residues"; every peptide has a N-terminus and C-terminus residue on the ends of the peptide (except for cyclic peptide
s). A polypeptide is a long, continuous, and unbranched peptide. Proteins consist of one or more polypeptides arranged in a biologically functional way and are often bound to cofactor
s, or other proteins.
The size boundaries which distinguish peptides, polypeptides, and proteins are arbitrary
. Long peptides such as amyloid beta
can be considered proteins, whereas small proteins such as insulin
can be considered peptides.
Milk peptides : Milk peptides are formed from milk proteins by enzymatic breakdown by digestive enzymes or by the proteinases formed by lactobacilli during the fermentation of milk. Several milk peptides have been shown to have antihypertensive effects in animal and in clinical studies (see also Lactotripeptides
).
Ribosomal peptides : Ribosomal peptides are synthesized by translation of mRNA. They are often subjected to proteolysis
to generate the mature form. These function, typically in higher organisms, as hormone
s and signaling molecules. Some organisms produce peptides as antibiotic
s, such as microcins
. Since they are translated, the amino acid
residues involved are restricted to those utilized by the ribosome. However, these peptides frequently have posttranslational modification
s, such as phosphorylation
, hydroxylation
, sulfonation, palmitylation, glycosylation and disulfide formation. In general, they are linear, although lariat
structures have been observed. More exotic manipulations do occur, such as racemization of L-amino acids to D-amino acids in platypus venom
.
Nonribosomal peptide
s : These peptides are assembled by enzyme
s that are specific to each peptide, rather than by the ribosome. The most common non-ribosomal peptide is glutathione
, which is a component of the antioxidant
defenses of most aerobic organisms. Other nonribosomal peptides are most common in unicellular organism
s, plant
s, and fungi and are synthesized by modular
enzyme complexes called nonribosomal peptide synthetases. These complexes are often laid out in a similar fashion, and they can contain many different modules to perform a diverse set of chemical manipulations on the developing product. These peptides are often cyclic
and can have highly-complex cyclic structures, although linear nonribosomal peptides are also common. Since the system is closely related to the machinery for building fatty acid
s and polyketide
s, hybrid compounds are often found. The presence of oxazoles or thiazoles often indicates that the compound was synthesized in this fashion.
Peptones
Peptide fragments : Peptide fragments refer to fragments of proteins that are used to identify or quantify the source protein. Often these are the products of enzymatic degradation performed in the laboratory on a controlled sample, but can also be forensic or paleontological samples that have been degraded by natural effects.
of interest. This involves synthesizing antigenic peptides of sections of the protein of interest. These will then be used to make antibodies in a rabbit or mouse against the protein.
Another reason is that peptides have become instrumental in mass spectrometry
, allowing the identification of proteins of interest based on peptide masses and sequence. In this case the peptides are most often generated by in-gel digestion
after electrophoretic
separation of the proteins.
Peptides have recently been used in the study of protein structure
and function. For example, synthetic peptides can be used as probes to see where protein-peptide interactions occur.
Inhibitory peptides are also used in clinical research to examine the effects of peptides on the inhibition of cancer proteins and other diseases.
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
s of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
s linked by peptide bond
Peptide bond
This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...
s. They are distinguished from protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptide
Dipeptide
A dipeptide is a molecule consisting of two amino acids joined by a single peptide bond.Dipeptides are produced from polypeptides by the action of the hydrolase enzyme dipeptidyl peptidase. Dietary proteins are digested to dipeptides and amino acids, and the dipeptides are absorbed more rapidly...
s, consisting of two amino acids joined by a single peptide bond. There are also tripeptide
Tripeptide
A tripeptide is a peptide consisting of three amino acids joined by peptide bonds.Examples of tripeptides are:*Eisenin is a peptide with immunological activity that is isolated from the Japanese marine alga, Eisenia bicyclis, which more commonly is known as, Arame*GHK-Cu is a human copper binding...
s, tetrapeptide
Tetrapeptide
A tetrapeptide is a peptide consisting of four amino acids joined by peptide bonds. Many tetrapeptides are pharmacologically active, often showing affinity and specificity for a variety of receptors in protein-protein signaling...
s, etc. Amino acids which have been incorporated into a peptide are termed "residues"; every peptide has a N-terminus and C-terminus residue on the ends of the peptide (except for cyclic peptide
Cyclic peptide
Cyclic peptides are polypeptide chains whose amino and carboxyl termini are themselves linked together with a peptide bond that forms a circular chain. A number of cyclic peptides have been discovered in nature and they can range anywhere from just a few amino acids in length, to hundreds...
s). A polypeptide is a long, continuous, and unbranched peptide. Proteins consist of one or more polypeptides arranged in a biologically functional way and are often bound to cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
s, or other proteins.
The size boundaries which distinguish peptides, polypeptides, and proteins are arbitrary
Arbitrary
Arbitrariness is a term given to choices and actions subject to individual will, judgment or preference, based solely upon an individual's opinion or discretion.Arbitrary decisions are not necessarily the same as random decisions...
. Long peptides such as amyloid beta
Amyloid beta
Amyloid beta is a peptide of 36–43 amino acids that is processed from the Amyloid precursor protein. While it is most commonly known in association with Alzheimer's disease, it does not exist specifically to cause disease...
can be considered proteins, whereas small proteins such as insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
can be considered peptides.
Peptide classes
Here are the major classes of peptides, according to how they are produced:Milk peptides : Milk peptides are formed from milk proteins by enzymatic breakdown by digestive enzymes or by the proteinases formed by lactobacilli during the fermentation of milk. Several milk peptides have been shown to have antihypertensive effects in animal and in clinical studies (see also Lactotripeptides
Lactotripeptides
Lactotripeptides are two naturally occurring milk peptides: Isoleucine-Proline-Proline and Valine-Proline-Proline . These lactotripeptides are derived from casein, which is a milk protein also found in dairy products. Although most normal dairy products contain lactotripeptides, they are inactive...
).
Ribosomal peptides : Ribosomal peptides are synthesized by translation of mRNA. They are often subjected to proteolysis
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
to generate the mature form. These function, typically in higher organisms, as hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s and signaling molecules. Some organisms produce peptides as antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s, such as microcins
Microcins
Microcins are very small bacteriocins, composed of a relatively few peptides. For this reason, they are distinct from their larger protein cousins. The classic example is microcin V, of E. coli....
. Since they are translated, the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
residues involved are restricted to those utilized by the ribosome. However, these peptides frequently have posttranslational modification
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
s, such as phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
, hydroxylation
Hydroxylation
Hydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...
, sulfonation, palmitylation, glycosylation and disulfide formation. In general, they are linear, although lariat
Lariat
Lariat can refer to:*A rope in the form of a lasso*Lariat chain, a science demonstration*A professional wrestling move, a variation of a clothesline*A genetic structure in Splicing *Double Lariat, a popular song sung by Luka Megurine...
structures have been observed. More exotic manipulations do occur, such as racemization of L-amino acids to D-amino acids in platypus venom
Platypus venom
The platypus is one of the few mammals to produce venom. Males have a pair of spurs on their hind limbs. The male's pair of spurs spits out a cocktail of poisons that, while excruciatingly painful, is not lethal to most animals.-Spur and crural gland:...
.
Nonribosomal peptide
Nonribosomal peptide
Nonribosomal peptides are a class of peptide secondary metabolites, usually produced by microorganisms like bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be made by bacteria inside these organisms...
s : These peptides are assembled by enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that are specific to each peptide, rather than by the ribosome. The most common non-ribosomal peptide is glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
, which is a component of the antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
defenses of most aerobic organisms. Other nonribosomal peptides are most common in unicellular organism
Unicellular organism
A unicellular organism, also known as a single-celled organism is an organism that consists of only one cell, in contrast to a multicellular organism that consists of multiple cells. Historically simple single celled organisms have sometimes been referred to as monads Prokaryotes, most protists,...
s, plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
s, and fungi and are synthesized by modular
Modularity (biology)
Many organisms consist of modules, both anatomically and in their metabolism. Anatomical modules are usually segments or organs. When we look at illustrations of metabolic reactions, we find that they, too, are modular: we can clearly identify, for instance, the citric acid cycle as a complex...
enzyme complexes called nonribosomal peptide synthetases. These complexes are often laid out in a similar fashion, and they can contain many different modules to perform a diverse set of chemical manipulations on the developing product. These peptides are often cyclic
Cyclic compound
In chemistry, a cyclic compound is a compound in which a series of atoms is connected to form a loop or ring.While the vast majority of cyclic compounds are organic, a few inorganic substances form cyclic compounds as well, including sulfur, silanes, phosphanes, phosphoric acid, and triboric acid. ...
and can have highly-complex cyclic structures, although linear nonribosomal peptides are also common. Since the system is closely related to the machinery for building fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s and polyketide
Polyketide
Polyketides are secondary metabolites from bacteria, fungi, plants, and animals. Polyketides are usually biosynthesized through the decarboxylative condensation of malonyl-CoA derived extender units in a similar process to fatty acid synthesis...
s, hybrid compounds are often found. The presence of oxazoles or thiazoles often indicates that the compound was synthesized in this fashion.
Peptones
-
- See also TryptoneTryptoneTryptone is the assortment of peptides formed by the digestion of casein by the protease trypsin.Tryptone is commonly used in microbiology to produce Lysogeny broth for the growth of E. coli and other microorganisms...
- See also Tryptone
- Peptones are derived from animal milk or meat digested by proteolytic digestion. In addition to containing small peptides, the resulting spray-dried material includes fats, metals, salts, vitamins and many other biological compounds. Peptone is used in nutrient media for growing bacteria and fungi.
Peptide fragments : Peptide fragments refer to fragments of proteins that are used to identify or quantify the source protein. Often these are the products of enzymatic degradation performed in the laboratory on a controlled sample, but can also be forensic or paleontological samples that have been degraded by natural effects.
Peptide synthesis
Peptides in molecular biology
Peptides have recently received prominence in molecular biology for several reasons. The first is that peptides allow the creation of peptide antibodies in animals without the need to purify the proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
of interest. This involves synthesizing antigenic peptides of sections of the protein of interest. These will then be used to make antibodies in a rabbit or mouse against the protein.
Another reason is that peptides have become instrumental in mass spectrometry
Mass spectrometry
Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...
, allowing the identification of proteins of interest based on peptide masses and sequence. In this case the peptides are most often generated by in-gel digestion
In-gel digestion
The in-gel digestion is part of the sample preparation for the mass spectrometric identification of proteins in course of proteomic analysis. The method was introduced 1992 by Rosenfeld...
after electrophoretic
Electrophoresis
Electrophoresis, also called cataphoresis, is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric field. This electrokinetic phenomenon was observed for the first time in 1807 by Reuss , who noticed that the application of a constant electric...
separation of the proteins.
Peptides have recently been used in the study of protein structure
Protein structure
Proteins are an important class of biological macromolecules present in all organisms. Proteins are polymers of amino acids. Classified by their physical size, proteins are nanoparticles . Each protein polymer – also known as a polypeptide – consists of a sequence formed from 20 possible L-α-amino...
and function. For example, synthetic peptides can be used as probes to see where protein-peptide interactions occur.
Inhibitory peptides are also used in clinical research to examine the effects of peptides on the inhibition of cancer proteins and other diseases.
Well-known peptide families in humans
The peptide families in this section are ribosomal peptides, usually with hormonal activity. All of these peptides are synthesized by cells as longer "propeptides" or "proproteins" and truncated prior to exiting the cell. They are released into the bloodstream where they perform their signalling functions.Tachykinin peptides
- Substance PSubstance PIn the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
- KassininKassininKassinin is a peptide derived from the Kassina frog....
- Neurokinin ANeurokinin ANeurokinin A is a member of the tachykinin family of neuropeptide neurotransmitters. It is produced from the same preprotachykinin A gene as the neuropeptide substance P. It has various roles in the body of humans and other animals...
- EledoisinEledoisinEledoisin is an undecapeptide of mollusk origin, belonging to the tachykinin family of neuropeptides.It was first isolated from the posterior salivary glands of two mollusk species Eledone muschata and Eledone aldovandi, which belong to the octopod order of Cephalopoda. Other tachykinins from...
- Neurokinin BNeurokinin BNeurokinin B is a tachykinin peptide.It is found in higher concentration in pregnant women suffering pre-eclampsia and can bind the immune-cloaking molecule phosphocholine....
Vasoactive intestinal peptides
- VIPVasoactive intestinal peptideVasoactive intestinal peptide also known as the vasoactive intestinal polypeptide or VIP is a peptide hormone containing 29 amino acid residues that is produced in many tissues of vertebrates including the gut, pancreas and suprachiasmatic nuclei of the hypothalamus in the brain...
(Vasoactive Intestinal Peptide; PHM27) - PACAPPituitary adenylate cyclase activating peptidePituitary adenylate cyclase-activating polypeptide also known as PACAP is a protein that in humans is encoded by the ADCYAP1 gene. PACAP is similar to vasoactive intestinal peptide. One of its effects is to stimulate enterochromaffin-like cells. It binds to vasoactive intestinal peptide receptor.-...
Pituitary Adenylate Cyclase Activating Peptide - Peptide PHIPeptide PHIPeptide PHI is a peptide which functions as a hormone.It plays a role in the regulation of prolactin in humans....
27 (Peptide Histidine Isoleucine 27) - GHRHGrowth hormone releasing hormoneGrowth-hormone-releasing hormone , also known as growth-hormone-releasing factor , somatoliberin or somatocrinin, is a releasing hormone for growth hormone...
1-24 (Growth Hormone Releasing Hormone 1-24) - GlucagonGlucagonGlucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
- SecretinSecretinSecretin is a hormone that controls the secretions into the duodenum, and also separately, water homeostasis throughout the body. It is produced in the S cells of the duodenum in the crypts of Lieberkühn...
Pancreatic polypeptide-related peptides
- NPY (NeuroPeptide Y)
- PYYPeptide YYPeptide YY is a short protein released by cells in the ileum and colon in response to feeding. In humans it appears to reduce appetite.It is also known as PYY, Peptide Tyrosine Tyrosine, or Pancreatic Peptide YY3-36....
(Peptide YY) - APP (Avian Pancreatic Polypeptide)
- PPYPancreatic polypeptidePancreatic polypeptide is a polypeptide secreted by PP cells in the endocrine pancreas predominantly in the head of the pancreas. It consists of 36 amino acids and has molecular weight about 4200 Da....
Pancreatic PolYpeptide
Opioid peptides
- ProopiomelanocortinProopiomelanocortinPro-opiomelanocortin is a precursor polypeptide with 241 amino acid residues. POMC is synthesized from the 285-amino acid long polypeptide precursor, pre-pro-opiomelanocortin , by the removal of a 44-amino acid long signal peptide sequence during translation.The POMC gene is located on chromosome...
(POMC) peptides - EnkephalinEnkephalinAn enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin were revealed, one...
pentapeptides - ProdynorphinProdynorphinProdynorphin, also known as proenkephalin B, is an opioid polypeptide hormone involved with chemical signal transduction and cell communication. The gene for prodynorphin is expressed in the endometrium and the striatum, and its gene map locus is 20pter-p12...
peptides
Other peptides
- B-type Natriuretic Peptide (BNP)Brain natriuretic peptideBrain natriuretic peptide , now known as B-type natriuretic peptide or GC-B, is a 32 amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of heart muscle cells...
- produced in myocardium & useful in medical diagnosis - LactotripeptidesLactotripeptidesLactotripeptides are two naturally occurring milk peptides: Isoleucine-Proline-Proline and Valine-Proline-Proline . These lactotripeptides are derived from casein, which is a milk protein also found in dairy products. Although most normal dairy products contain lactotripeptides, they are inactive...
- Lactotripeptides might reduce blood pressureBlood pressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, although the evidence is mixed.
See also
- ArgirelineArgirelineAcetyl hexapeptide-3 is a synthetic anti-wrinkle cosmetics ingredient. It is a peptide which is a shortened version of Botulinum toxin...
- Bis-peptideBis-peptideBis-peptides are analogues of peptides, but consist of bis-amino acids, which bear two carboxyl groups and two amino groups. The connection of specific bis-amino acids leads to the formation of bis-peptides with well-defined molecular shape, which is of great interest for designing...
- Epidermal Growth FactorEpidermal growth factorEpidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...
- Journal of Peptide ScienceJournal of Peptide ScienceThe Journal of Peptide Science is a monthly peer-reviewed scientific journal, published since 1995 by John Wiley & Sons on behalf of the European Peptide Society. The current editor-in-chief is Luis Moroder ....
- LactotripeptidesLactotripeptidesLactotripeptides are two naturally occurring milk peptides: Isoleucine-Proline-Proline and Valine-Proline-Proline . These lactotripeptides are derived from casein, which is a milk protein also found in dairy products. Although most normal dairy products contain lactotripeptides, they are inactive...
- Pancreatic hormonePancreatic hormonePancreatic hormones are peptides synthesized in pancreatic islets of Langerhans, which acts as a regulator of pancreatic and gastrointestinal functions....
- Peptide Spectral LibraryPeptide Spectral LibraryPeptide Spectral Library is a curated, annotated and non-redundant collection/database of LC-MS/MS peptide spectra. One essential utility of Peptide Spectral Library is to serve as consensus templates supporting the identification of peptide/proteins based on the correlation between the templates...
- Peptide synthesisPeptide synthesisIn organic chemistry, peptide synthesis is the production of peptides, which are organic compounds in which multiple amino acids are linked via amide bonds which are also known as peptide bonds...
- PeptidomimeticPeptidomimeticA peptidomimetic is a small protein-like chain designed to mimic a peptide. They typically arise either from modification of an existing peptide, or by designing similar systems that mimic peptides, such as peptoids and β-peptides...
s (such as peptoidPeptoidPeptoids, or poly-N-substituted glycines, are a class of peptidomimetics whose side chains are appended to the nitrogen atom of the peptide backbone, rather than to the α-carbons .-Chemical structure and synthesis:...
s and β-peptideBeta-peptideβ-peptides consist of β amino acids, which have their amino group bonded to the β carbon rather than the α carbon as in the 20 standard biological amino acids. The only commonly naturally occurring β amino acid is β-alanine; although it is used as a component of larger bioactive molecules,...
s) to peptides, but with different properties. - RibosomeRibosomeA ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
- TranslationTranslation (genetics)In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
- Beefy meaty peptideBeefy meaty peptideBeefy meaty peptide, also known as delicious peptide and abbreviated as BMP, is an 8-amino acid long peptide that has been identified as giving a beefy flavor to foods in which it is present. It was isolated from beef soup by Yamasaki and Maekawa....