Dehydroalanine: Difference between revisions

| 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 =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| CASNo_Ref = {{cascite|correct|??}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 98RA387EKY

| PubChem=123991

| ChEBI_Ref = {{ebicite|correct|EBI}}

| Formula=C₃H₅NO₂

| MolarMass=87.08 g/mol

| Appearance=

| Density=

| MeltingPt=

| BoilingPtC=

| Solubility=

| MainHazards=

| FlashPt=

| AutoignitionPt =

'''Dehydroalanine''' ('''Cα,β-didehydroalanine''', '''α,β-di-dehydroalanine''', '''2-aminoacrylate''', or '''2,3-didehydroalanine''') is a [[dehydroamino acid]]. It does not exist in its free form, but it occurs naturally as a residue found in [[peptide]]s of [[Microorganism|microbial]] origin.<ref>{{cite journal |last1=Downs |first1=DM |last2=Ernst |first2=DC |title=From microbiology to cancer biology: the Rid protein family prevents cellular damage caused by endogenously generated reactive nitrogen species. |journal=Molecular Microbiology |date=April 2015 |volume=96 |issue=2 |pages=211–9 |doi=10.1111/mmi.12945 |pmid=25620221|pmc=4974816 }}</ref> As an amino acid residue, it is unusual because it has an [[Saturated and unsaturated compounds|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 [[enamine]]s, dehydroalanine is unstable. Dehydroalanine hydrolyzes to [[pyruvate]].

''N''-Acylated derivatives of dehydroalanine, such as peptides and related compounds, are stable. For example, [[methyl 2-acetamidoacrylate]] is the N-acetylated derivative of the ester. As a residue in a peptide, it 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 [[nucleophile]]s, but those containing dehydroalanine or some other dehydroamino acids are exceptions. These are [[electrophilic]] due to the [[Carbonyl group#α,β-Unsaturated carbonyl compounds|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==

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 [[microcystin]]s.

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-link]]s and [[racemic|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-4H-imidazol-4-one|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+ }}</ref>

== Chemical synthesis ==

N-Acyl dehydroalanine derivatives have been synthesized by dehydration of serines using a [[Tert-butoxycarbonyl|''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=Gunnoo |first2=Smita B. |last3=Boutureira |first3=Omar |last4=Gerstberger |first4=Stefanie C. |last5=Fernández-González |first5=Marta |last6=Bernardes |first6=Gonçalo J. L. |last7=Griffin |first7=Laura |last8=Hailu |first8=Hanna |last9=Schofield |first9=Christopher J. |last10=Davis |first10=Benjamin G. |date=2011 |title=Methods for converting cysteine to dehydroalanine on peptides and proteins |url=http://xlink.rsc.org/?DOI=c1sc00185j |journal=Chemical Science |language=en |volume=2 |issue=9 |pages=1666 |doi=10.1039/c1sc00185j |issn=2041-6520}}</ref>

Newest methods allow the gram-scale synthesis of various protected dehydroamino acids by [[electrochemical]] oxidation of the respective amino acid derivative in methanol, followed by acid-catalyzed elimination of 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}}</ref>

==References==

<references />

[[Category:Alpha-Amino acids]]

[[Category:Non-proteinogenic amino acids]]