Editing Cross-link (section)

===Proteins===
In [[proteins]], crosslinks are important in generating mechanically stable structures such as [[hair]] and [[wool]], [[skin]], and [[cartilage]]. [[Disulfide bond]]s are common crosslinks.<ref>{{cite book |doi=10.1002/0471238961.2315151214012107.a01.pub2 |chapter=Wool |title=Kirk-Othmer Encyclopedia of Chemical Technology |date=2005 |last1=Christoe |first1=John R. |last2=Denning |first2=Ron J. |last3=Evans |first3=David J. |last4=Huson |first4=Mickey G. |last5=Jones |first5=Leslie N. |last6=Lamb |first6=Peter R. |last7=Millington |first7=Keith R. |last8=Phillips |first8=David G. |last9=Pierlot |first9=Anthony P. |last10=Rippon |first10=John A. |last11=Russell |first11=Ian M. |isbn=9780471484943 }}</ref>  [[Isopeptide bond]] formation is another type of protein crosslink.

The process of applying a [[permanent wave]] to hair involves the breaking and reformation of disulfide bonds. Typically a mercaptan such as ammonium thioglycolate is used for the breaking. Following this, the hair is curled and then "neutralized". The neutralizer is typically an acidic solution of hydrogen peroxide, which causes new disulfide bonds to form, thus permanently fixing the hair into its new configuration.

Compromised [[collagen]] in the cornea, a condition known as [[keratoconus]], can be treated with clinical crosslinking.<ref>Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7.</ref>
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It also happens for [[gluten]] which change structure of foods.
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In biological context crosslinking could play a role in [[atherosclerosis]] through [[advanced glycation end-product]]s (AGEs), which have been implicated to induce crosslinking of collagen, which may lead to vascular stiffening.<ref>{{cite journal|last1=Prasad|first1=Anand|last2=Bekker|first2=Peter|last3=Tsimikas|first3=Sotirios|date=2012-08-01|title=Advanced glycation end products and diabetic cardiovascular disease|journal=Cardiology in Review|volume=20|issue=4|pages=177–183|doi=10.1097/CRD.0b013e318244e57c|issn=1538-4683|pmid=22314141|s2cid=8471652}}</ref>

====Research====
Proteins can also be cross-linked artificially using small-molecule crosslinkers.  This approach has been used to elucidate [[protein–protein interaction]]s.<ref>{{cite web|url=http://www.piercenet.com/Objects/View.cfm?type=Page&ID=FE7F690D-58AE-4342-AE85-BA94DCA642F8|title=Pierce Protein Biology - Thermo Fisher Scientific|website=www.piercenet.com|access-date=1 April 2018}}</ref><ref name="Kou Qin">{{cite journal |author1=Kou Qin |author2=Chunmin Dong |author3=Guangyu Wu |author4=Nevin A Lambert |date=August 2011 |title= Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers |journal= Nature Chemical Biology |volume= 7 |issue= 11 |pages= 740–747 |doi=10.1038/nchembio.642 |pmid=21873996 |pmc=3177959}}</ref><ref>{{Cite journal|last1=Mizsei|first1=Réka|last2=Li|first2=Xiaolong|last3=Chen|first3=Wan-Na|last4=Szabo|first4=Monika|last5=Wang|first5=Jia-huai|last6=Wagner|first6=Gerhard|last7=Reinherz|first7=Ellis L.|last8=Mallis|first8=Robert J.|date=January 2021|title=A general chemical crosslinking strategy for structural analyses of weakly interacting proteins applied to preTCR-pMHC complexes|journal=Journal of Biological Chemistry|volume=296|pages=100255|doi=10.1016/j.jbc.2021.100255|pmid=33837736|pmc=7948749|issn=0021-9258|doi-access=free}}</ref> Crosslinkers bind only surface residues in relatively close proximity in the [[native state]]. Common crosslinkers include the [[imidoester]] crosslinker dimethyl suberimidate, the [[N-Hydroxysuccinimide]]-ester crosslinker [[bisSulfosuccinimidyl suberate|BS3]] and [[formaldehyde]]. Each of these crosslinkers induces nucleophilic attack of the amino group of [[lysine]] and subsequent covalent bonding via the crosslinker. The zero-length [[carbodiimide]] crosslinker [[Carbodiimide#EDC|EDC]] functions by converting carboxyls into amine-reactive isourea intermediates that bind to lysine residues or other available primary amines. SMCC or its water-soluble analog, Sulfo-SMCC, is commonly used to prepare antibody-hapten conjugates for antibody development.

An ''in-vitro'' cross-linking method is PICUP ([[photo-induced cross-linking of unmodified proteins]]).<ref name=":0">{{cite journal|last1=Fancy|first1=David A.|last2=Kodadek|first2=Thomas|date=1999-05-25|title=Chemistry for the analysis of protein–protein interactions: Rapid and efficient cross-linking triggered by long wavelength light|journal=Proceedings of the National Academy of Sciences|language =en|volume=96|issue=11|pages=6020–6024|doi=10.1073/pnas.96.11.6020|issn=0027-8424|pmid=10339534|pmc=26828|bibcode=1999PNAS...96.6020F|doi-access=free}}</ref> Typical reagents are [[ammonium persulfate]] (APS), an electron acceptor, the photosensitizer [[tris(bipyridine)ruthenium(II) chloride|tris-bipyridylruthenium (II) cation]] ({{chem2|[Ru(bpy)3](2+)}}).<ref name=":0"/> In ''in-vivo'' crosslinking of protein complexes, cells are grown with [[photoreactive]] [[diazirine]] analogs to [[leucine]] and [[methionine]], which are incorporated into proteins. Upon exposure to ultraviolet light, the diazirines are activated and bind to interacting proteins that are within a few [[ångström]]s of the photo-reactive amino acid analog (UV cross-linking).<ref>{{cite journal |last=Suchanek |first=Monika |author2=Anna Radzikowska |author3=Christoph Thiele |title=Photo-leucine and photo-methionine allow identification of protein–protein interactions in living cells |journal=Nature Methods |volume=2 |issue=4 |pages=261–268 |date=April 2005 |pmid=15782218 |doi= 10.1038/nmeth752|doi-access=free }}</ref>