Editing Peptide bond

{{short description|Covalent chemical bond between amino acids in a peptide or protein chain}}
[[File:Peptide bond.png|thumb|right|Peptide bond]]

In [[organic chemistry]], a '''peptide bond''' is an [[amide]] type of [[Covalent bond|covalent]] [[chemical bond]] linking two consecutive [[alpha-amino acid]]s from C1 ([[carbon]] number one) of one alpha-amino acid and N2 ([[nitrogen]] number two) of another, along a [[peptide]] or [[protein]] chain.<ref name=":0">{{Cite journal |date=1984 |title=Nomenclature and Symbolism for Amino Acids and Peptides. Recommendations 1983 |journal=European Journal of Biochemistry |volume=138 |issue=1 |pages=9–37 |doi=10.1111/j.1432-1033.1984.tb07877.x |issn=0014-2956 |pmid=6692818 |doi-access=free}}</ref>

It can also be called a '''eupeptide bond'''<ref name=":0" /> to distinguish it from an [[isopeptide bond]], which is another type of amide bond between two amino acids.

==Synthesis==
[[File:Peptidformationball.svg|thumb|right|Peptide bond formation via [[dehydration reaction]]]]
When two amino acids form a ''[[dipeptide]]'' through a ''peptide bond'',<ref name=":0" /> it is a type of [[condensation reaction]].<ref>{{Cite journal |last=Muller |first=P. |date=1994-01-01 |title=Glossary of terms used in physical organic chemistry (IUPAC Recommendations 1994) |journal=Pure and Applied Chemistry |volume=66 |issue=5 |pages=1077–1184 |doi=10.1351/pac199466051077 |s2cid=195819485 |issn=1365-3075|url=https://archive-ouverte.unige.ch/unige:151920 |doi-access=free }}</ref> In this kind of condensation, two amino acids approach each other, with the non-[[side chain]] (C1) [[carboxylic acid]] [[Functional group|moiety]] of one coming near the non-side chain (N2) [[amino]] moiety of the other. One loses a [[hydrogen]] and oxygen from its carboxyl group (COOH) and the other loses a hydrogen from its amino group (NH<sub>2</sub>). This reaction produces a molecule of water (H<sub>2</sub>O) and two amino acids joined by a peptide bond (−CO−NH−). The two joined amino acids are called a dipeptide.

The amide bond is synthesized when the [[carboxyl group]] of one amino acid molecule reacts with the [[amino group]] of the other amino acid molecule, causing the release of a molecule of [[water]] (H<sub>2</sub>O), hence the process is a [[dehydration synthesis]] reaction.
[[File:AminoacidCondensation.svg|thumb|center|The dehydration condensation of two [[amino acid]]s to form a peptide bond (red) with expulsion of water (blue)|590x590px]]
The formation of the peptide bond consumes energy, which, in organisms, is derived from [[Adenosine triphosphate|ATP]].<ref>{{cite book |last1=Watson |first1=James |last2=Hopkins |first2=Nancy |last3=Roberts |first3=Jeffrey |last4=Agetsinger Steitz |first4=Joan |last5=Weiner |first5=Alan |year=1987 |orig-date=1965 |title=Molecualar Biology of the Gene |type=hardcover |edition=Fourth |location=Menlo Park, CA |publisher=The Benjamin/Cummings Publishing Company, Inc. |page=[https://archive.org/details/molecularbiology0004unse/page/168 168] |isbn=978-0-8053-9614-0 |url=https://archive.org/details/molecularbiology0004unse/page/168 }}</ref> Peptides and [[protein]]s are chains of [[amino acid]]s held together by peptide bonds (and sometimes by a few [[isopeptide bond]]s). Organisms use [[enzyme]]s to produce [[nonribosomal peptide]]s,<ref>{{cite book |author=Miller B. R. |author2=Gulick A. M. | title = Nonribosomal Peptide and Polyketide Biosynthesis | chapter = Structural Biology of Nonribosomal Peptide Synthetases | series = Methods in Molecular Biology | volume = 1401 | pages = 3–29 | date = 2016 | pmid = 26831698 | pmc = 4760355 | doi = 10.1007/978-1-4939-3375-4_1 | isbn = 978-1-4939-3373-0 }}</ref> and [[ribosome]]s to produce proteins via reactions that differ in details from dehydration synthesis.<ref>{{cite book |author=Griffiths A. J. |author2=Miller J. H. |author3=Suzuki D. T. |author4=Lewontin R. C. |author5=Gelbart W. M. |date=2000 |title=Protein synthesis |url=https://www.ncbi.nlm.nih.gov/books/NBK22022/ |journal=An Introduction to Genetic Analysis |edition=7th | location = New York | publisher =  W. H. Freeman |isbn=978-0-7167-3520-5 }}</ref>

Some peptides, like [[alpha-amanitin]], are called ribosomal peptides as they are made by ribosomes,<ref>{{cite journal |author=Walton J. D. |author2=Hallen-Adams H. E. |author3=Luo H. | title = Ribosomal biosynthesis of the cyclic peptide toxins of Amanita mushrooms | journal = Biopolymers | volume = 94 | issue = 5 | pages = 659–664 | date = 2010 | pmid = 20564017 | pmc = 4001729 | doi = 10.1002/bip.21416 }}</ref> but many are [[nonribosomal peptide]]s as they are synthesized by specialized enzymes rather than ribosomes. For example, the tripeptide [[glutathione]] is synthesized in two steps from free [[amino acid]]s, by two [[enzyme]]s: [[glutamate–cysteine ligase]] (forms an [[isopeptide bond]], which is not a peptide bond) and [[glutathione synthetase]] (forms a peptide bond).<ref>{{cite journal |author=Wu G. |author2=Fang Y. Z. |author3=Yang S. |author4=Lupton J. R. |author5=Turner N. D. | title = Glutathione metabolism and its implications for health | journal = The Journal of Nutrition | volume = 134 | issue = 3 | pages = 489–492 | date = March 2004 | pmid = 14988435 | doi = 10.1093/jn/134.3.489 | doi-access = free }}</ref><ref>{{cite journal |author=Meister A. | title = Glutathione metabolism and its selective modification | journal = The Journal of Biological Chemistry | volume = 263 | issue = 33 | pages = 17205–17208 | date = November 1988 | pmid = 3053703 | doi = 10.1016/S0021-9258(19)77815-6 | url = https://www.jbc.org/article/S0021-9258(19)77815-6/fulltext | doi-access = free }}</ref>

==Degradation==
A peptide bond can be broken by [[hydrolysis]] (the addition of water). The hydrolysis of peptide bonds in water releases 8–16&nbsp;[[joule|kJ]]/[[mole (unit)|mol]] (2–4&nbsp;[[calorie|kcal]]/[[mole (unit)|mol]]) of [[Gibbs energy]].<ref>{{cite journal |author=Martin R. B. | date = December 1998 | title = Free energies and equilibria of peptide bond hydrolysis and formation | journal = Biopolymers | volume = 45 | issue = 5 | pages = 351–353 | doi = 10.1002/(SICI)1097-0282(19980415)45:5<351::AID-BIP3>3.0.CO;2-K }}</ref> This process is extremely slow, with the [[half life]] at 25&nbsp;°C of between 350 and 600 years per bond.<ref>{{cite journal |last1=Radzicka |first1=Anna |last2=Wolfenden |first2=Richard |date=1996-01-01 |title=Rates of Uncatalyzed Peptide Bond Hydrolysis in Neutral Solution and the Transition State Affinities of Proteases |journal=Journal of the American Chemical Society |volume=118 |issue=26 |pages=6105–6109 |doi=10.1021/ja954077c |issn=0002-7863}}</ref>

In living organisms, the process is normally [[catalysis|catalyzed]] by [[enzyme]]s known as peptidases or [[protease]]s, although there are reports of peptide bond hydrolysis caused by conformational strain as the peptide/protein folds into the native structure.<ref name="pmid18308334">{{cite journal |author=Sandberg A. |author2=Johansson D. G. |author3=Macao B. |author4=Härd T. | title = SEA domain autoproteolysis accelerated by conformational strain: energetic aspects | journal = Journal of Molecular Biology | volume = 377 | issue = 4 | pages = 1117–1129 | date = April 2008 | pmid = 18308334 | doi = 10.1016/j.jmb.2008.01.051 }}</ref> This non-enzymatic process is thus not accelerated by transition state stabilization, but rather by ground-state destabilization.

==Spectra==
The [[wavelength]] of absorption for a peptide bond is 190–230&nbsp;nm,<ref name="pmid14907727">{{cite journal |author=Goldfarb A. R. |author2=Saidel L. J. |author3=Mosovich E. | title = The ultraviolet absorption spectra of proteins | journal = The Journal of Biological Chemistry | volume = 193 | issue = 1 | pages = 397–404 | date = November 1951 | doi = 10.1016/S0021-9258(19)52465-6 | pmid = 14907727 | url = http://www.jbc.org/content/193/1/397.long | doi-access = free }}</ref> which makes it particularly susceptible to [[UV]] radiation.

==Cis/trans isomers of the peptide group==

Significant delocalisation of the [[lone pair]] of electrons on the nitrogen atom gives the group a [[Amide#Structure and bonding|partial double-bond]] character. The partial double bond renders the amide group [[Plane (geometry)|planar]], occurring in either the [[Cis-trans isomerism|cis]] or [[trans isomer]]s. In the unfolded state of proteins, the peptide groups are free to isomerize and adopt both isomers; however, in the folded state, only a single isomer is adopted at each position (with rare exceptions). The trans form is preferred overwhelmingly in most peptide bonds (roughly 1000:1 ratio in trans:cis populations).  However, X-Pro peptide groups tend to have a roughly 30:1 ratio, presumably because the symmetry between the C<sup>α</sup> and C<sup>δ</sup> atoms of [[proline]] makes the cis and trans isomers nearly equal in energy, as shown in the figure below.
[[Image:Cis trans isomerization kinetics X Pro peptide bonds.png|thumb|center|alt=Diagram of the isomerization of an X-Pro peptide bond. The diagram shows the cis isomer on the left, the transition states in the center, and the trans isomer on the right, with bidirectional arrows between each pair of states.|Isomerization of an X-Pro peptide bond. Cis and trans isomers are at far left and far right, respectively, separated by the transition states.|500x500px]]
The [[dihedral angle]] associated with the peptide group (defined by the four atoms C<sup>α</sup>–C'–N–C<sup>α</sup>) is denoted <math>\omega</math>; <math>\omega = 0^\circ</math> for the cis isomer ([[synperiplanar]] conformation), and <math>\omega = 180^\circ</math> for the trans isomer ([[antiperiplanar]] conformation). Amide groups can isomerize about the C'–N bond between the cis and trans forms, albeit slowly (<math>\tau \sim 20</math>&nbsp;seconds at room temperature). The [[transition state]]s <math>\omega = \pm 90^\circ</math> require that the partial double bond be broken, so that the activation energy is roughly 80&nbsp;kJ/mol (20&nbsp;kcal/mol). However, the [[activation energy]] can be lowered (and the isomerization [[catalysis|catalyzed]]) by changes that favor the single-bonded form, such as placing the peptide group in a hydrophobic environment or donating a hydrogen bond to the nitrogen atom of an X-Pro peptide group. Both of these mechanisms for lowering the activation energy have been observed in ''peptidyl prolyl isomerases'' (PPIases), which are naturally occurring enzymes that catalyze the cis-trans isomerization of X-Pro peptide bonds.

Conformational [[protein folding]] is usually much faster (typically 10–100&nbsp;ms) than cis-trans isomerization (10–100&nbsp;s). A nonnative isomer of some peptide groups can disrupt the conformational folding significantly, either slowing it or preventing it from even occurring until the native isomer is reached. However, not all peptide groups have the same effect on folding; nonnative isomers of other peptide groups may not affect folding at all.

==Chemical reactions==
Due to its resonance stabilization, the peptide bond is relatively unreactive under physiological conditions, even less than similar compounds such as [[ester]]s. Nevertheless, peptide bonds can undergo chemical reactions, usually through an attack of an [[electronegativity|electronegative]] atom on the [[carbonyl]] [[carbon]], breaking the carbonyl double bond and forming a tetrahedral intermediate. This is the pathway followed in [[proteolysis]] and, more generally, in N–O acyl exchange reactions such as those of [[intein]]s. When the functional group attacking the peptide bond is a [[thiol]], [[hydroxyl]] or [[amine]], the resulting molecule may be called a [[cyclol]] or, more specifically, a thiacyclol, an oxacyclol or an azacyclol, respectively.

== See also ==
* [[The Proteolysis Map]]

== References ==
{{Reflist}}

{{Chemical bonds}}
{{Protein primary structure}}
{{Authority control}}

[[Category:Protein structure]]
[[Category:Chemical bonding]]