Editing Peptide synthesis (section)

====Carbodiimides====
[[File:DIC HOBt coupling.svg|thumb|[[Amide]] bond formation using DIC/HOBt.<ref name="Montalbetti05" />]]
[[Carbodiimide]]s such as [[dicyclohexylcarbodiimide]] (DCC) and [[diisopropylcarbodiimide]] (DIC) are frequently used for amide bond formation.<ref name="Montalbetti05" /> The reaction proceeds via the formation of a highly reactive ''O''-acyliso[[urea]]. This reactive intermediate is attacked by the peptide N-terminal amine, forming a peptide bond. Formation of the ''O''-acyliso[[urea]] proceeds fastest in non-polar solvents such as dichloromethane.<ref>{{Cite journal|vauthors=Singh S|date=January 2018|title=CarboMAX - Enhanced Peptide Coupling at Elevated Temperatures|url=https://cem.com/media/contenttype/media/literature/ap0124v2-cem.pdf|journal=AP Note|volume=0124|pages=1–5|archive-date=6 August 2020|access-date=7 August 2018|archive-url=https://web.archive.org/web/20200806041631/https://cem.com/media/contenttype/media/literature/ap0124v2-cem.pdf|url-status=dead}}</ref>

DIC is particularly useful for SPPS since as a liquid it is easily dispensed, and the [[urea]] byproduct is easily washed away. Conversely, the related carbodiimide [[1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide]] (EDC) is often used for solution-phase peptide couplings as its urea byproduct can be removed by washing during aqueous [[Work-up (chemistry)|work-up]].<ref name="Montalbetti05" />

[[File:HOBT.png|thumb|left|100px|HOBt]]
[[File:1-hydroxy-7-aza-benzotriazole.svg|thumb|100px|left|HOAt]]
[[File:HOAt neighbouring.gif|thumb|200px|right|Neighbouring group effect of HOAt]]

Carbodiimide activation opens the possibility for [[racemization]] of the activated amino acid.<ref name="Montalbetti05" /> Racemization can be circumvented with 'racemization suppressing' additives such as the [[triazole]]s [[hydroxybenzotriazole|1-hydroxy-benzotriazole]] (HOBt), and [[1-Hydroxy-7-azabenzotriazole|1-hydroxy-7-aza-benzotriazole]] (HOAt). These reagents attack the ''O''-acylisourea intermediate to form an [[active ester]], which subsequently reacts with the peptide to form the desired peptide bond.<ref name=Joullié>{{cite journal | vauthors = Joullié MM, Lassen KM |journal=Arkivoc|year=2010|volume=viii|pages=189–250|title=Evolution of Amide Bond Formation |issue=8 |doi=10.3998/ark.5550190.0011.816 |url=http://www.arkat-usa.org/get-file/34631/|doi-access=free|hdl=2027/spo.5550190.0011.816|hdl-access=free}}</ref> [[Ethyl cyanohydroxyiminoacetate]] (Oxyma), an additive for carbodiimide coupling, acts as an alternative to HOAt.<ref name="subiros09">{{cite journal | vauthors = Subirós-Funosas R, Prohens R, Barbas R, El-Faham A, Albericio F | title = Oxyma: an efficient additive for peptide synthesis to replace the benzotriazole-based HOBt and HOAt with a lower risk of explosion | journal = Chemistry: A European Journal | volume = 15 | issue = 37 | pages = 9394–9403 | date = September 2009 | pmid = 19575348 | doi = 10.1002/chem.200900614 | ref = subiros09 }}</ref>