{{chembox | verifiedrevid = 443736092 | ImageFile = Dehydroalanin.svg | ImageSize = 150px | ImageName = Structural formula | ImageFile1 = Dehydroalanine-zwitterion-3D-balls.png | ImageSize1 = 150px | ImageName1 = Ball-and-stick model of the zwitterion | PIN = 2-Aminoprop-2-enoic acid | OtherNames = Cα,β-didehydroalanine, α,β-didehydroalanine, 2-aminoacrylate, 2,3-didehydroalanine |Section1={{Chembox Identifiers | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 110510 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C02218 | InChI = 1/C3H5NO2/c1-2(4)3(5)6/h1,4H2,(H,5,6) | InChIKey = UQBOJOOOTLPNST-UHFFFAOYAW | SMILES1 = O=C(O)C(=C)N | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C3H5NO2/c1-2(4)3(5)6/h1,4H2,(H,5,6) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = UQBOJOOOTLPNST-UHFFFAOYSA-N | CASNo_Ref = {{cascite|correct|??}} | CASNo=1948-56-7 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 98RA387EKY | PubChem=123991 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 17123 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB02688 | SMILES=C=C(C(=O)O)N }} |Section2={{Chembox Properties | Formula=C<sub>3</sub>H<sub>5</sub>NO<sub>2</sub> | MolarMass=87.08 g/mol | Appearance= | Density= | MeltingPt= | BoilingPtC= | Solubility= }} |Section3={{Chembox Hazards | MainHazards= | FlashPt= | AutoignitionPt = }} }}
'''Dehydroalanine''' is an organic compound with the formula {{chem2|CH2\dCH(NH2)CO2H}}. It does not exist in its free form, but it occurs naturally as a residue found in peptides of microbial origin. Unlike most amino acid residues, it has an unsaturated backbone.<ref name=DS>{{cite journal |first= Dawid |last= Siodłak |title= α,β-Dehydroamino Acids in Naturally Occurring Peptides |journal= Amino Acids |year= 2015 |volume= 47 |issue= 1 |pages= 1–17 |doi= 10.1007/s00726-014-1846-4 |pmid= 25323736 |pmc= 4282715 }}</ref>
==Structure and reactivity== Like most primary enamines, dehydroalanine is unstable. It would hydrolyze to pyruvate:<ref name=Asq/> :{{chem2|CH2\dCH(NH2)CO2H + H2O -> CH3\sC(O)CO2H + NH3}} ''N''-Acylated derivatives of dehydroalanine, such as are found peptides and related compounds, are stable. One such example is methyl 2-acetamidoacrylate.<ref name=Asq2/> As a residue in a peptide, dehydroalanine is generated by a post translational modification. The required precursors are serine or cysteine residues, which undergo enzyme-mediated loss of water and hydrogen sulfide, respectively.
Most amino acid residues are unreactive toward nucleophiles, but those containing dehydroalanine or some other dehydroamino acids are exceptions. These residues are electrophilic due to the α,β-unsaturated carbonyl,<ref name=DS/> and can, for example, alkylate other amino acids.<!-- see next section for example --> This activity has made DHA useful synthetically to prepare lanthionine.
==Occurrence== Dehydroalanine had been proposed as early as 1937, but it was established by analysis of the reactions of base with glutathione.<ref name=Asq>{{cite journal |last1=Asquith |first1=R.S. |last2=Carthew |first2=P. |title=The preparation and subsequent identification of a dehydroalanyl peptide from alkali-treated oxidised glutathione |journal=Biochimica et Biophysica Acta (BBA) - Protein Structure |date=1972 |volume=285 |issue=2 |pages=346–351 |doi=10.1016/0005-2795(72)90319-4 |pmid=4659645 }}</ref> Alkaline degradation of cystine-containing peptides and proteins was shown to give derivatives containing lanthionine and lysinoalanine. N-acetyldehydroglycine was also shown to add amines.<ref name=Asq2>{{cite journal |last1=Asquith |first1=R.S. |last2=Carthew |first2=P. |title=Synthesis and PMR properties of some dehydroalanine derivatives |journal=Tetrahedron |date=1972 |volume=28 |issue=18 |pages=4769–4773 |doi=10.1016/0040-4020(72)88085-2}}</ref>
The dehydroalanine residue was first detected in nisin, a cyclic peptide with antimicrobial activity.<ref name="DS" /> Dehydroalanine is also present in some lantibiotics and microcystins.
DHA can be formed from cysteine or serine by simple base catalysis without the need for an enzyme, which can happen during cooking and alkaline food preparation processes. It can then alkylate other amino acid residues, such as lysine, forming lysinoalanine cross-links and racemization of the original alanine. The resulting proteins have lower nutritional quality for some species but higher nutritional quality for others. Some lysinoalanines may also cause kidney enlargement in rats.<ref>{{cite book |title= Impact of Processing on Food Safety |year= 1999 |volume= 459 |pages= 145–159 |chapter= Lysinoalanine in food and in antimicrobial proteins |first= Mendel |last= Friedman |pmid= 10335374 |doi= 10.1007/978-1-4615-4853-9_10 |editor1-first= Lauren S. |editor1-last= Jackson |editor2-first= Mark G. |editor2-last= Knize |editor3-first= Jeffrey N. |editor3-last= Morgan |publisher= Springer |isbn= 978-1-4615-4853-9 |series= Advances in Experimental Medicine and Biology }}</ref>
Many dehydroalanine-containing peptides are toxic.<ref name=DS/> [[File:Nisin.png|left|thumb|444 px|The antimicrobial bacteriocin nisin contains three dehydro amino acid residues, two of which are dehydroalanine residues.]] A dehydroalanine residue was long thought to be an important electrophilic catalytic residue in histidine ammonia-lyase and phenylalanine ammonia-lyase enzymes, but the active residue was later found instead to be a different unsaturated alanine derivative — 3,5-dihydro-5-methyldiene-4''H''-imidazol-4-one — that is even more electrophilic.<ref>{{cite journal |journal= Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics |title= Discovery and role of methylidene imidazolone, a highly electrophilic prosthetic group |first=János |last= Rétey |year= 2003 |volume= 1647 |issue= 1–2 |pages= 179–184 |doi= 10.1016/S1570-9639(03)00091-8 |pmid= 12686130 }}</ref><ref>{{cite journal | vauthors = Calabrese JC, Jordan DB, Boodhoo A, Sariaslani S, Vannelli T | title = Crystal structure of phenylalanine ammonia lyase: multiple helix dipoles implicated in catalysis | journal = Biochemistry | volume = 43 | issue = 36 | pages = 11403–16 | date = September 2004 | pmid = 15350127 | doi = 10.1021/bi049053+ | bibcode = 2004Bioc...4311403C }}</ref>
== Chemical synthesis == N-Acyl dehydroalanine derivatives have been synthesized by dehydration of serines using a ''tert''-butoxycarbonate leaving group,<ref>{{Cite journal |last1=Ferreira |first1=Paula M. T. |last2=Maia |first2=Hernâni L. S. |last3=Monteiro |first3=Luís S. |last4=Sacramento |first4=Joana |date=1999 |title=High yielding synthesis of dehydroamino acid and dehydropeptide derivatives |url=http://xlink.rsc.org/?DOI=a904730a |journal=Journal of the Chemical Society, Perkin Transactions 1 |issue=24 |pages=3697–3703 |doi=10.1039/a904730a|hdl=1822/2188 |hdl-access=free }}</ref> or by conversion of Cysteine derivatives using various reagents for the elimination of the Thiol-group.<ref>{{cite journal|last1=Chalker |first1=Justin M. |last2=Bernardes |first2=Gonçalo J. L. |last3=Davis |first3=Benjamin G. |title=A "Tag-and-Modify" Approach to Site-Selective Protein Modification |journal=Accounts of Chemical Research |date=2011 |volume=44 |issue=9 |pages=730–741 |doi=10.1021/ar200056q |pmid=21563755 }}</ref> Various protected dehydroamino acids can be produced by electrochemical oxidation of the respective amino acid derivative in methanol.<ref>{{Cite journal |last1=Gausmann |first1=Marcel |last2=Kreidt |first2=Nadine |last3=Christmann |first3=Mathias |date=2023-04-07 |title=Electrosynthesis of Protected Dehydroamino Acids |url=https://pubs.acs.org/doi/10.1021/acs.orglett.3c00403 |journal=Organic Letters |language=en |volume=25 |issue=13 |pages=2228–2232 |doi=10.1021/acs.orglett.3c00403 |pmid=36952622 |s2cid=257716096 |issn=1523-7060|url-access=subscription }}</ref>
Dehydroalanine derivatives have proven to be useful in late-stage peptide modification, enabling straightforward synthesis of functionally diverse peptides or proteins.<ref>{{cite journal|last1=Dadová |first1=Jitka |last2=Galan |first2=Sébastien RG |last3=Davis |first3=Benjamin G. |title=Synthesis of modified proteins via functionalization of dehydroalanine |journal=Current Opinion in Chemical Biology |date=2018 |volume=46 |pages=71–81 |doi=10.1016/j.cbpa.2018.05.022 |pmid=29913421 |doi-access=free }}</ref><ref>{{Cite journal |last=Yu |first=Changjun |last2=Bao |first2=Guangjun |last3=Sun |first3=Wangsheng |date=2025-10-31 |title=Recent Advances on Dehydroalanine‐Specific Modification and Diversification of Peptides and Proteins |url=https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202500349 |journal=ChemBioChem |language=en |volume=26 |issue=20 |doi=10.1002/cbic.202500349 |issn=1439-4227|url-access=subscription }}</ref>
==References== <references />
Category:Alpha-Amino acids Category:Non-proteinogenic amino acids