A peptide bond is a chemical bond that is formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H₂O). This is a dehydration synthesis reaction (also known as a condensation reaction), and usually occurs between amino acids. The resulting CO-NH bond is called a peptide bond, and the resulting molecule is an amide. The four-atom functional group -C(=O)NH- is called an amide group or (in the context of proteins) a peptide group. Polypeptides and proteins are chains of amino acids held together by peptide bonds, as is the backbone of PNA. Polyamides, such as nylons and aramids, are synthetic molecules (polymers) that possess peptide bonds. A chemical bond is the physical process responsible for the attractive interactions between atoms and molecules, and that which confers stability to diatomic and polyatomic chemical compounds. ... 3D (left and center) and 2D (right) representations of the terpenoid molecule atisane. ... In chemistry, a carboxyl group is a functional group consisting of a carbon atom doubly bonded to an oxygen atom and single-bonded to a hydroxyl (-OH) group, typically written as -COOH: where R is a hydrogen or an organic group. ... The general structure of an amine Amines are organic compounds and a type of functional group that contain nitrogen as the key atom. ... Impact from a water drop causes an upward rebound jet surrounded by circular capillary waves. ... Dehydration synthesis is a type of synthesis reaction in which two smaller molecules are joined together by a covalent bond and water is formed (released) in the reaction. ... A condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule. ... Phenylalanine is one of the standard amino acids. ... Amide functional group Amides possess a conjugated system spread over the O, C and N atoms, consisting of molecular orbitals occupied by delocalized electrons. ... Peptides are the family of molecules formed from the linking, in a defined order, of various amino acids. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Phenylalanine is one of the standard amino acids. ... PNA can also refer to the Palestinian National Authority or Pakistan National Alliance. ... A polyamide is a polymer containing monomers joined by peptide bonds. ... For other uses of this word, see nylon (disambiguation). ... Aramid fiber (1961) is a fire-resistant and strong synthetic fiber. ... A polymer (from Greek: πολυ, polu, many; and μέρος, meros, part) is a substance composed of molecules with large molecular mass composed of repeating structural units, or monomers, connected by covalent chemical bonds. ...

Figure 1: Dehydration synthesis (condensation) reaction forming an amide

Figure 2: Resonance forms of a typical peptide group. The uncharged, single-bonded form (typically ~60%) is shown on the left, whereas the charged, double-bonded form (typically ~40%) is on the right.

Figure 3: Donation of an H-bond to an X-Pro peptide group favors the single-bonded resonance form (left) over the double-bonded form (right).

Figure 4: An electronegative substituent near the amide nitrogen favors the single-bonded resonance form (left) over the double-bonded form (right).

A peptide bond can be broken by amide hydrolysis (the adding of water). The peptide bonds in proteins are metastable, meaning that in the presence of water they will break spontaneously, releasing about 10 kJ/mol of free energy, but this process is extremely slow. In living organisms, the process is facilitated by enzymes. Living organisms also employ enzymes to form peptide bonds; this process requires free energy. The wavelength of absorbance for a peptide bond is 190-230nm. This image is ineligible for copyright and therefore in the public domain, because it consists entirely of information that is common property and contains no original authorship. ... Image File history File links Peptide_group_resonance. ... Image File history File links Prolyl_peptide_group_resonance. ... Image File history File links Prolyl_peptide_group_resonance_electronegative. ... Amide hydrolysis involves the C-N bond being broken in reaction with water (hydrolysis). ... Metastability is the ability of a non-equilibrium state to persist for a long period of time. ... The joule (IPA: or ) (symbol: J) is the SI unit of energy. ... The mole (symbol: mol) is the SI base unit that measures an amount of substance. ... The free energy is a measure of the amount of mechanical (or other) work that can be extracted from a system, and is helpful in engineering applications. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... The wavelength is the distance between repeating units of a wave pattern. ... In spectroscopy, the absorbance A is defined as , where I is the intensity of light at a specified wavelength λ that has passed through a sample (transmitted light intensity) and is the intensity of the light before it enters the sample (or incident light intensity). ...

Resonance forms of the peptide group

The amide group has two resonance forms, which confer several important properties. First, it stabilizes the group by roughly 20 kcal/mol, making it less reactive than many similar groups (such as esters). The resonance suggests that the amide group has a partial double bond character, estimated at 40% under typical conditions. The peptide group is uncharged at all normal pH values, but its double-bonded resonance form gives it a unusually large dipole moment, roughly 3.5 Debye (0.7 electron-angstrom). These dipole moments can line up in certain secondary structures (such as the α-helix), producing a large net dipole. Resonance in chemistry is a tool used to represent and model certain types of non-classical molecular structures. ... A carboxylic acid ester. ... “Covalent” redirects here. ... A representation of the 3D structure of the Myoglobin protein. ...

The partial double bond character can be strengthened or weakened by modifications that favor one resonance form over another. For example, the double-bonded form is disfavored in hydrophobic environments, because of its charge. Conversely, donating a hydrogen bond to the amide oxygen or accepting a hydrogen bond from the amide nitrogen should favor the double-bonded form, because the hydrogen bond should be stronger to the charged form than to the uncharged, single-bonded form. By contrast, donating a hydrogen bond to an amide nitrogen in an X-Pro peptide bond should favor the single-bonded form; donating it to the double-bonded form would give the nitrogen five quasi-covalent bonds! (See Figure 3.) Similarly, a strongly electronegative substituent (such as fluorine) near the amide nitrogen favors the single-bonded form, by competing with the amide oxygen to "steal" an electron from the amide nitrogen (See Figure 4.) In chemistry, hydrophobic or lipophilic species, or hydrophobes, tend to be electrically neutral and nonpolar, and thus prefer other neutral and nonpolar solvents or molecular environments. ... An example of a quadruple hydrogen bond between a self-assembled dimer complex reported by Meijer and coworkers. ... General Name, symbol, number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, period, block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... Proline is an α-amino acid with the chemical formula HO2CCH(NH[CH2)3]. L-Proline is one of the twenty DNA-encoded amino acids. ... Electronegativity is a measure of the ability of an atom or molecule to attract electrons in the context of a chemical bond. ... Distinguished from fluorene and fluorone. ... General Name, symbol, number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, period, block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ...

Cis/trans isomers of the peptide group

The partial double bond renders the amide group planar, occurring in either the cis or trans isomers. 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 3:1 ratio, presumably because the symmetry between the C^α and C^δ atoms of proline makes the cis and trans isomers nearly equal in energy (See figure, below). CIS usually refers to: Commonwealth of Independent States, a modern-day political entity consisting of 11 former Soviet Union Republics CIS is also an acronym for: Canadian Interuniversity Sport Cancer Information Service Carcinoma in situ Centre for Independent Studies Center for Immigration Studies Chinese International School Cisalpino Citizenship & Immigration Services... Trans is a Latin noun or prefix, meaning across, beyond or on the opposite side [of] . It is the opposite of cis, which means on the same side [of]. In chemistry, a double bond (or ring) not subject to free rotation in which the greater radical on both ends is...

Isomerization of an X-Pro peptide bond. Cis and trans isomers are at far left and far right, respectively, separated by the transition states.

The dihedral angle associated with the peptide group (defined by the four atoms ) is denoted ω; for the cis isomer and for the trans isomer. Amide groups can isomerize about the C-N bond between the cis and trans forms, albeit slowly (20 seconds at room temperature). The transition states requires that the partial double bond be broken, so that the activation energy is roughly 20 kcal/mol (See Figure below). However, the activation energy can be lowered (and the isomerization 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. Image File history File links Cis_trans_isomerization_kinetics_X_Pro_peptide_bonds. ... In Aerospace engineering, the dihedral is the angle that the two wings make with each other. ... CIS usually refers to: Commonwealth of Independent States, a modern-day political entity consisting of 11 former Soviet Union Republics CIS is also an acronym for: Canadian Interuniversity Sport Cancer Information Service Carcinoma in situ Centre for Independent Studies Center for Immigration Studies Chinese International School Cisalpino Citizenship & Immigration Services... Trans is a Latin noun or prefix, meaning across, beyond or on the opposite side [of] . It is the opposite of cis, which means on the same side [of]. In chemistry, a double bond (or ring) not subject to free rotation in which the greater radical on both ends is... CIS usually refers to: Commonwealth of Independent States, a modern-day political entity consisting of 11 former Soviet Union Republics CIS is also an acronym for: Canadian Interuniversity Sport Cancer Information Service Carcinoma in situ Centre for Independent Studies Center for Immigration Studies Chinese International School Cisalpino Citizenship & Immigration Services... Trans is a Latin noun or prefix, meaning across, beyond or on the opposite side [of] . It is the opposite of cis, which means on the same side [of]. In chemistry, a double bond (or ring) not subject to free rotation in which the greater radical on both ends is... The transition state of a chemical reaction is a particular configuration along the reaction coordinate. ... The sparks generated by striking steel against a flint provide the activation energy to initiate combustion in this Bunsen burner. ... In chemistry and biology, catalysis is the acceleration (increase in rate) of a chemical reaction by means of a substance, called a catalyst, that is itself not consumed by the overall reaction. ...

Conformational protein folding is usually much faster (typically 10-100 ms) than cis-trans isomerization (10-100 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. Protein folding is the process by which a protein assumes its characteristic functional shape or tertiary structure, also known as the native state. ...

Chemical reactions

Owing to its resonance stabilization, the peptide bond is relatively unreactive under physiological conditions, even less than similar compounds such as esters. Nevertheless, peptide bonds can undergo chemical reactions, usually through an attack of an 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 inteins. 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. A carboxylic acid ester. ... Electronegativity is a measure of the ability of an atom or molecule to attract electrons in the context of a chemical bond. ... Carbonyl group In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom : C=O. The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex (a metal carbonyl, e. ... For other uses, see Carbon (disambiguation). ... Proteolysis is the directed degradation (digestion) of proteins by cellular enzymes called proteases or by intramolecular digestion. ... An intein is a segment of a protein that is able to excise itself and rejoin the remaining portions (the exteins) with a peptide bond. ... Sulphydryl // In organic chemistry, a thiol is a compound that contains the functional group composed of a sulfur atom and a hydrogen atom (-SH). ... // Hydroxyl group The term hydroxyl group is used to describe the functional group -OH when it is a substituent in an organic compound. ... The general structure of an amine Amines are organic compounds and a type of functional group that contain nitrogen as the key atom. ... Figure 1: In the classic cyclol reaction, two peptide groups are linked by a N-C’ bond, converting the carbonyl oxygen into a hydroxyl group. ...

References

• Pauling L. (1960) The Nature of the Chemical Bond, 3rd. ed., Cornell University Press. ISBN 0-8014-0333-2

• Stein RL. (1993) "Mechanism of Enzymatic and Nonenzymatic Prolyl cis-trans Isomerization", Adv. Protein Chem., 44, 1-24.

• Schmid FX, Layr LM, Mücke M and Schönbrunner ER. (1993) "Prolyl Isomerases: Role in Protein Folding", Adv. Protein Chem., 44, 25-66.

• Fischer G. (1994) "Peptidyl-Prolyl cis/trans Isomerases and Their Effectors", Angew. Chem. Int. Ed. Engl., 33, 1415-1436.