# Dehydroalanine

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Dehydroalanine
> Markdown URL: https://mediated.wiki/source/Dehydroalanine.md
> Source: https://en.wikipedia.org/wiki/Dehydroalanine
> Source revision: 1343757586
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{{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](/source/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 [peptide](/source/peptide)s of [microbial](/source/Microorganism) origin.  Unlike most amino acid residues, it has an [unsaturated](/source/Saturated_and_unsaturated_compounds) 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 [enamine](/source/enamine)s, dehydroalanine is unstable.  It would hydrolyze to [pyruvate](/source/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](/source/methyl_2-acetamidoacrylate).<ref name=Asq2/>  As a residue in a peptide, dehydroalanine is generated by a [post translational modification](/source/post_translational_modification).  The required precursors are [serine](/source/serine) or [cysteine](/source/cysteine) residues, which undergo enzyme-mediated loss of water and [hydrogen sulfide](/source/hydrogen_sulfide), respectively.

Most amino acid residues are unreactive toward [nucleophile](/source/nucleophile)s, but those containing dehydroalanine or some other dehydroamino acids are exceptions. These residues are [electrophilic](/source/electrophilic) due to the [α,β-unsaturated carbonyl](/source/Carbonyl_group),<ref name=DS/> and can, for example, [alkylate](/source/alkylate) other amino acids.<!-- see next section for example --> This activity has made DHA useful synthetically to prepare [lanthionine](/source/lanthionine).

==Occurrence==
Dehydroalanine had been proposed as early as 1937, but it was established by analysis of the reactions of base with [glutathione](/source/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](/source/cystine)-containing peptides and proteins was shown to give derivatives containing [lanthionine](/source/lanthionine) and [lysinoalanine](/source/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](/source/nisin), a [cyclic peptide](/source/cyclic_peptide) with antimicrobial activity.<ref name="DS" /> Dehydroalanine is also present in some [lantibiotics](/source/lantibiotics) and [microcystin](/source/microcystin)s.

DHA can be formed from [cysteine](/source/cysteine) or [serine](/source/serine) by simple base catalysis without the need for an enzyme, which can happen during cooking and [alkaline](/source/alkaline) food preparation processes. It can then alkylate other amino acid residues, such as [lysine](/source/lysine), forming lysinoalanine [cross-link](/source/cross-link)s and [racemization](/source/racemic) 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](/source/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](/source/catalytic_residue) in [histidine ammonia-lyase](/source/histidine_ammonia-lyase) and [phenylalanine ammonia-lyase](/source/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](/source/3%2C5-dihydro-5-methyldiene-4H-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](/source/Tert-butoxycarbonyl) 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](/source/Cysteine) derivatives using various reagents for the elimination of the [Thiol](/source/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](/source/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

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Adapted from the Wikipedia article [Dehydroalanine](https://en.wikipedia.org/wiki/Dehydroalanine) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Dehydroalanine?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.