KAHA Ligation
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KAHA Ligation
The α-Ketoacid-Hydroxylamine (KAHA) Amide-Forming Ligation is a chemical reaction that is used to join two unprotected fragments in peptide synthesis.{{cite journal, last1=Pusterla, first1=Ivano, last2=Bode, first2=Jeffrey W., title=The Mechanism of the α-Ketoacid-Hydroxylamine Amide-Forming Ligation, journal=Angewandte Chemie, volume=124, issue=2, year=2012, pages=528–531, issn=0044-8249, doi=10.1002/ange.201107198 It is an alternative to the Native Chemical Ligation (NCL). KAHA Ligation was developed by Jeffrey W. Bode group at ETH Zürich (previously University of Pennsylvania). Overview An α-ketoacid at the C-terminus of one peptide fragment reacts with a hydroxylamine at the N-terminus of another to form a peptide bond (amide bond). The reaction can happen in the presence of unprotected side chains, and it does not require any coupling reagents or catalysts. The only byproducts are water and CO2. The first reported protein synthesized by KAHA ligation was huma ...
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Peptide Synthesis
In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxyl group of one amino acid to the amino group of another. Protecting group strategies are usually necessary to prevent undesirable side reactions with the various amino acid side chains. Chemical peptide synthesis most commonly starts at the carboxyl end of the peptide (C-terminus), and proceeds toward the amino-terminus (N-terminus). Protein biosynthesis (long peptides) in living organisms occurs in the opposite direction. The chemical synthesis of peptides can be carried out using classical solution-phase techniques, although these have been replaced in most research and development settings by solid-phase methods (see below). Solution-phase synthesis retains its usefulness in large-scale production of peptides for industrial purposes how ...
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Native Chemical Ligation
Native Chemical Ligation (NCL) is an important extension of the chemical ligation concept for constructing a larger polypeptide chain by the covalent condensation of two or more unprotected peptides segments. Native chemical ligation is the most effective method for synthesizing native or modified proteins of typical size (''i.e.'', proteins< ~300 AA).


Reaction

In native chemical ligation, the ionized group of an residue of an unprotected peptide attacks the

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ETH Zürich
(colloquially) , former_name = eidgenössische polytechnische Schule , image = ETHZ.JPG , image_size = , established = , type = Public , budget = CHF 1.896 billion (2021) , rector = Günther Dissertori , president = Joël Mesot , academic_staff = 6,612 (including doctoral students, excluding 527 professors of all ranks, 34% female, 65% foreign nationals) (full-time equivalents 2021) , administrative_staff = 3,106 (40% female, 19% foreign nationals, full-time equivalents 2021) , students = 24,534 (headcount 2021, 33.3% female, 37% foreign nationals) , undergrad = 10,642 , postgrad = 8,299 , doctoral = 4,460 , other = 1,133 , address = Rämistrasse 101CH-8092 ZürichSwitzerland , city = Zürich , coor = , campus = Urban , language = German, English (Masters and upwards, sometimes Bachelor) , affiliations = CESAER, EUA, GlobalTech, IARU, IDEA League, UNITECH , website ethz.ch, colors = Black and White , logo = ETH Zürich Logo black.svg ETH Zür ...
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Ketoacid
In organic chemistry, keto acids or ketoacids (also called oxo acids or oxoacids) are organic compounds that contain a carboxylic acid group () and a ketone group ().Franz Dietrich Klingler, Wolfgang Ebertz "Oxocarboxylic Acids" in Ullmann's Encyclopedia of Industrial Chemistry 2005, Wiley-VCH, Weinheim. In several cases, the keto group is hydrated. The alpha-keto acids are especially important in biology as they are involved in the Krebs citric acid cycle and in glycolysis. Common types of keto acids include: *Alpha-keto acids, alpha-ketoacids, or 2-oxoacids have the keto group adjacent to the carboxylic acid. They often arise by oxidative deamination of amino acids, and reciprocally, they are precursors to the same. Alpha-keto acids possesses extensive chemistry as acylation agents. Furthermore, alpha-keto acids such as phenylpyruvic acid are endogenous sources for carbon monoxide (as a gasotransmitter) and pharmaceutical prodrug scaffold. Important representatives: ...
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C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus. The convention for writing peptide sequences is to put the C-terminal end on the right and write the sequence from N- to C-terminus. Chemistry Each amino acid has a carboxyl group and an amine group. Amino acids link to one another to form a chain by a dehydration reaction which joins the amine group of one amino acid to the carboxyl group of the next. Thus polypeptide chains have an end with an unbound carboxyl group, the C-terminus, and an end with an unbound amine group, the N-terminus. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus. Function C-terminal retention signals While the N-terminus of a protein often co ...
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Hydroxylamine
Hydroxylamine is an inorganic compound with the formula . The material is a white crystalline, hygroscopic compound.Greenwood and Earnshaw. ''Chemistry of the Elements.'' 2nd Edition. Reed Educational and Professional Publishing Ltd. pp. 431–432. 1997. Hydroxylamine is almost always provided and used as an aqueous solution. It is consumed almost exclusively to produce Nylon-6. It is also an intermediate in biological nitrification. The oxidation of to hydroxylamine is a step in biological nitrification. History Hydroxylamine was first prepared as hydroxylammonium chloride in 1865 by the German chemist Wilhelm Clemens Lossen (1838-1906); he reacted tin and hydrochloric acid in the presence of ethyl nitrate. It was first prepared in pure form in 1891 by the Dutch chemist Lobry de Bruyn and by the French chemist Léon Maurice Crismer (1858-1944). The coordination complex , known as Crismer's salt, releases hydroxylamine upon heating. Production Hydroxylamine or its salts can be ...
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N-terminus
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amine group is bonded to the carboxylic group of another amino acid, making it a chain. That leaves a free carboxylic group at one end of the peptide, called the C-terminus, and a free amine group on the other end called the N-terminus. By convention, peptide sequences are written N-terminus to C-terminus, left to right (in LTR writing systems). This correlates the translation direction to the text direction, because when a protein is translated from messenger RNA, it is created from the N-terminus to the C-terminus, as amino acids are added to the carboxyl end of the protein. Chemistry Each amino acid has an amine group and a carboxylic group. Amino acids link to one another by peptide bonds which form through a dehydration reaction ...
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Peptide Bond
In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 ( nitrogen number two) of another, along a peptide or protein chain. It can also be called a eupeptide bond to distinguish it from an isopeptide bond, which is another type of amide bond between two amino acids. Synthesis When two amino acids form a '' dipeptide'' through a ''peptide bond'', it is a type of condensation reaction. In this kind of condensation, two amino acids approach each other, with the non- side chain (C1) carboxylic acid moiety of one coming near the non-side chain (N2) amino moiety of the other. One loses a hydrogen and oxygen from its carboxyl group (COOH) and the other loses a hydrogen from its amino group (NH2). This reaction produces a molecule of water (H2O) and two amino acids joined by a peptide bond (−CO−NH−). The two joined amino acids are called a dipeptide. ...
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Catalyst
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quickly, very small amounts of catalyst often suffice; mixing, surface area, and temperature are important factors in reaction rate. Catalysts generally react with one or more reactants to form intermediates that subsequently give the final reaction product, in the process of regenerating the catalyst. Catalysis may be classified as either homogeneous, whose components are dispersed in the same phase (usually gaseous or liquid) as the reactant, or heterogeneous, whose components are not in the same phase. Enzymes and other biocatalysts are often considered as a third category. Catalysis is ubiquitous in chemical industry of all kinds. Estimates are that 90% of all commercially produced chemical products involve catalysts at some sta ...
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KAHA Ligation Type I
Kaha may refer to: Places * Kaha, Iran, a village in Hormozgan Province, Iran * Kaha, Kalbajar, a village in the Kalbajar District, Azerbaijan * Kaha, Lachin, a village in the Lachin District, Azerbaijan * Kaha, Parang, a barangay in Parang, Sulu, Philippines * Te Kaha, a town in New Zealand * Kaha-ri, a district of Usi province, North Korea * Qaha, a city in Egypt, often spelt ''Kaha'' Other * Kaha (Māori), a Māori term roughly translating as strength ** Kia kaha, a Māori term of affirmation or support * Daniel Kaha (born 1989), Israeli footballer * HMNZS ''Te Kaha'' (F77), a New Zealand naval frigate * Ka-Ha, a type of Chinese armoured vehicle * KAHA- a Hawaiian radio station now broadcasting as KPOI-FM *''Kaha'' is also a Sanskrit Sanskrit (; attributively , ; nominally , , ) is a classical language belonging to the Indo-Aryan branch of the Indo-European languages. It arose in South Asia after its predecessor languages had diffused there from the northwest in th ...
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GLP-1
Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region. Alongside glucose-dependent insulinotropic peptide (GIP), GLP-1 is an incretin; thus, it has the ability to decrease blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin. Beside the insulinotropic effects, GLP-1 has been associated with numerous regulatory and protective e ...
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