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Structural formula of proline Prolin - Proline.svg
Structural formula of proline
IUPAC name
Systematic IUPAC name
Pyrrolidine-2-carboxylic acid [1]
3D model (JSmol)
ECHA InfoCard 100.009.264 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • L:210-189-3
MeSH Proline
PubChem CID
RTECS number
  • L:TW3584000
  • InChI=1S/C5H9NO2/c7-5(8)4-2-1-3-6-4/h4,6H,1-3H2,(H,7,8)/t4-/m0/s1 Yes check.svgY
  • L:C1C[C@H](NC1)C(=O)O
  • L Zwitterion:[O-]C(=O)[C@H](CCC2)[NH2+]2
Molar mass 115.132 g·mol−1
AppearanceTransparent crystals
Melting point 205 to 228 °C (401 to 442 °F; 478 to 501 K) (decomposes)
Solubility 1.5g/100g ethanol 19 degC [2]
log P -0.06
Acidity (pKa)1.99 (carboxyl), 10.96 (amino) [3]
Supplementary data page
Proline (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Proline (symbol Pro or P) [4] is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group -NH
but is rather a secondary amine. The secondary amine nitrogen is in the protonated form (NH2+) under biological conditions, while the carboxyl group is in the deprotonated −COO form. The "side chain" from the α carbon connects to the nitrogen forming a pyrrolidine loop, classifying it as a aliphatic amino acid. It is non-essential in humans, meaning the body can synthesize it from the non-essential amino acid L-glutamate. It is encoded by all the codons starting with CC (CCU, CCC, CCA, and CCG).


Proline is the only proteinogenic secondary amino acid which is a secondary amine, as the nitrogen atom is attached both to the α-carbon and to a chain of three carbons that together form a five-membered ring.

History and etymology

Proline was first isolated in 1900 by Richard Willstätter who obtained the amino acid while studying N-methylproline, and synthesized proline by the reaction of sodium salt of diethyl malonate with 1,3-dibromopropane. The next year, Emil Fischer isolated proline from casein and the decomposition products of γ-phthalimido-propylmalonic ester, [5] and published the synthesis of proline from phthalimide propylmalonic ester. [6]

The name proline comes from pyrrolidine, one of its constituents. [7]


Proline is biosynthetically derived from the amino acid L-glutamate. Glutamate-5-semialdehyde is first formed by glutamate 5-kinase (ATP-dependent) and glutamate-5-semialdehyde dehydrogenase (which requires NADH or NADPH). This can then either spontaneously cyclize to form 1-pyrroline-5-carboxylic acid, which is reduced to proline by pyrroline-5-carboxylate reductase (using NADH or NADPH), or turned into ornithine by ornithine aminotransferase, followed by cyclisation by ornithine cyclodeaminase to form proline. [8]

Zwitterionic structure of both proline enantiomers: (S)-proline (left) and (R)-proline Betain-Proline.png
Zwitterionic structure of both proline enantiomers: (S)-proline (left) and (R)-proline

Biological activity

L-Proline has been found to act as a weak agonist of the glycine receptor and of both NMDA and non-NMDA (AMPA/kainate) ionotropic glutamate receptors. [9] [10] [11] It has been proposed to be a potential endogenous excitotoxin. [9] [10] [11] In plants, proline accumulation is a common physiological response to various stresses but is also part of the developmental program in generative tissues (e.g. pollen). [12] [13] [14] [15]

A diet rich in proline was linked to an increased risk of depression in humans in a study from 2022 that was tested on a limited pre-clinical trial on humans and primarily in other organisms. Results were significant in the other organisms. [16]

Properties in protein structure

The distinctive cyclic structure of proline's side chain gives proline an exceptional conformational rigidity compared to other amino acids. It also affects the rate of peptide bond formation between proline and other amino acids. When proline is bound as an amide in a peptide bond, its nitrogen is not bound to any hydrogen, meaning it cannot act as a hydrogen bond donor, but can be a hydrogen bond acceptor.

Peptide bond formation with incoming Pro-tRNAPro is considerably slower than with any other tRNAs, which is a general feature of N-alkylamino acids. [17] Peptide bond formation is also slow between an incoming tRNA and a chain ending in proline; with the creation of proline-proline bonds slowest of all. [18]

The exceptional conformational rigidity of proline affects the secondary structure of proteins near a proline residue and may account for proline's higher prevalence in the proteins of thermophilic organisms. Protein secondary structure can be described in terms of the dihedral angles φ, ψ and ω of the protein backbone. The cyclic structure of proline's side chain locks the angle φ at approximately −65°. [19]

Proline acts as a structural disruptor in the middle of regular secondary structure elements such as alpha helices and beta sheets; however, proline is commonly found as the first residue of an alpha helix and also in the edge strands of beta sheets. Proline is also commonly found in turns (another kind of secondary structure), and aids in the formation of beta turns. This may account for the curious fact that proline is usually solvent-exposed, despite having a completely aliphatic side chain.

Multiple prolines and/or hydroxyprolines in a row can create a polyproline helix, the predominant secondary structure in collagen. The hydroxylation of proline by prolyl hydroxylase (or other additions of electron-withdrawing substituents such as fluorine) increases the conformational stability of collagen significantly. [20] Hence, the hydroxylation of proline is a critical biochemical process for maintaining the connective tissue of higher organisms. Severe diseases such as scurvy can result from defects in this hydroxylation, e.g., mutations in the enzyme prolyl hydroxylase or lack of the necessary ascorbate (vitamin C) cofactor.

Cistrans isomerization

Peptide bonds to proline, and to other N-substituted amino acids (such as sarcosine), are able to populate both the cis and trans isomers. Most peptide bonds overwhelmingly adopt the trans isomer (typically 99.9% under unstrained conditions), chiefly because the amide hydrogen (trans isomer) offers less steric repulsion to the preceding Cα atom than does the following Cα atom (cis isomer). By contrast, the cis and trans isomers of the X-Pro peptide bond (where X represents any amino acid) both experience steric clashes with the neighboring substitution and have a much lower energy difference. Hence, the fraction of X-Pro peptide bonds in the cis isomer under unstrained conditions is significantly elevated, with cis fractions typically in the range of 3-10%. [21] However, these values depend on the preceding amino acid, with Gly [22] and aromatic [23] residues yielding increased fractions of the cis isomer. Cis fractions up to 40% have been identified for aromatic–proline peptide bonds. [24]

From a kinetic standpoint, cistrans proline isomerization is a very slow process that can impede the progress of protein folding by trapping one or more proline residues crucial for folding in the non-native isomer, especially when the native protein requires the cis isomer. This is because proline residues are exclusively synthesized in the ribosome as the trans isomer form. All organisms possess prolyl isomerase enzymes to catalyze this isomerization, and some bacteria have specialized prolyl isomerases associated with the ribosome. However, not all prolines are essential for folding, and protein folding may proceed at a normal rate despite having non-native conformers of many X–Pro peptide bonds.


Proline and its derivatives are often used as asymmetric catalysts in proline organocatalysis reactions. The CBS reduction and proline catalysed aldol condensation are prominent examples.

In brewing, proteins rich in proline combine with polyphenols to produce haze (turbidity). [25]

L-Proline is an osmoprotectant and therefore is used in many pharmaceutical and biotechnological applications.

The growth medium used in plant tissue culture may be supplemented with proline. This can increase growth, perhaps because it helps the plant tolerate the stresses of tissue culture. [26] [ better source needed ] For proline's role in the stress response of plants, see § Biological activity.


Proline is one of the two amino acids that do not follow along with the typical Ramachandran plot, along with glycine. Due to the ring formation connected to the beta carbon, the ψ and φ angles about the peptide bond have fewer allowable degrees of rotation. As a result, it is often found in "turns" of proteins as its free entropy (ΔS) is not as comparatively large to other amino acids and thus in a folded form vs. unfolded form, the change in entropy is smaller. Furthermore, proline is rarely found in α and β structures as it would reduce the stability of such structures, because its side chain α-nitrogen can only form one nitrogen bond.

Additionally, proline is the only amino acid that does not form a red-purple colour when developed by spraying with ninhydrin for uses in chromatography. Proline, instead, produces an orange-yellow colour.


Racemic proline can be synthesized from diethyl malonate and acrylonitrile: [27]

DL-Proline synth.png

See also

Related Research Articles

<span class="mw-page-title-main">Amino acid</span> Organic compounds containing amine and carboxylic groups

Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code.

<span class="mw-page-title-main">Alpha helix</span> Type of secondary structure of proteins

The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earlier along the protein sequence.

<span class="mw-page-title-main">Beta sheet</span> Protein structural motif

The beta sheet, (β-sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet. A β-strand is a stretch of polypeptide chain typically 3 to 10 amino acids long with backbone in an extended conformation. The supramolecular association of β-sheets has been implicated in the formation of the fibrils and protein aggregates observed in amyloidosis, notably Alzheimer's disease.

<span class="mw-page-title-main">Collagen helix</span> Main protein structure of fibrous collagen

In molecular biology, the collagen triple helix or type-2 helix is the main secondary structure of various types of fibrous collagen, including type I collagen. In 1954, Ramachandran & Kartha advanced a structure for the collagen triple helix on the basis of fiber diffraction data. It consists of a triple helix made of the repetitious amino acid sequence glycine-X-Y, where X and Y are frequently proline or hydroxyproline. Collagen folded into a triple helix is known as tropocollagen. Collagen triple helices are often bundled into fibrils which themselves form larger fibres, as in tendons.

<span class="mw-page-title-main">Peptide bond</span> Covalent chemical bond between amino acids in a peptide or protein chain

In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 of one alpha-amino acid and N2 of another, along a peptide or protein chain.

<span class="mw-page-title-main">Protein primary structure</span> Linear sequence of amino acids in a peptide or protein

Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthesis is most commonly performed by ribosomes in cells. Peptides can also be synthesized in the laboratory. Protein primary structures can be directly sequenced, or inferred from DNA sequences.

<span class="mw-page-title-main">Hydroxyproline</span> Chemical compound

(2S,4R)-4-Hydroxyproline, or L-hydroxyproline (C5H9O3N), is an amino acid, abbreviated as Hyp or O, e.g., in Protein Data Bank.

<span class="mw-page-title-main">Enoyl CoA isomerase</span>

Enoyl-CoA-(∆) isomerase (EC, also known as dodecenoyl-CoA- isomerase, 3,2-trans-enoyl-CoA isomerase, ∆3 ,∆2 -enoyl-CoA isomerase, or acetylene-allene isomerase, is an enzyme that catalyzes the conversion of cis- or trans-double bonds of coenzyme A bound fatty acids at gamma-carbon to trans double bonds at beta-carbon as below:

Peptoids, or poly-N-substituted glycines, are a class of biochemicals known as biomimetics that replicate the behavior of biological molecules. Peptidomimetics are recognizable by side chains that are appended to the nitrogen atom of the peptide backbone, rather than to the α-carbons.

A turn is an element of secondary structure in proteins where the polypeptide chain reverses its overall direction.

A polyproline helix is a type of protein secondary structure which occurs in proteins comprising repeating proline residues. A left-handed polyproline II helix is formed when sequential residues all adopt (φ,ψ) backbone dihedral angles of roughly and have trans isomers of their peptide bonds. This PPII conformation is also common in proteins and polypeptides with other amino acids apart from proline. Similarly, a more compact right-handed polyproline I helix is formed when sequential residues all adopt (φ,ψ) backbone dihedral angles of roughly and have cis isomers of their peptide bonds. Of the twenty common naturally occurring amino acids, only proline is likely to adopt the cis isomer of the peptide bond, specifically the X-Pro peptide bond; steric and electronic factors heavily favor the trans isomer in most other peptide bonds. However, peptide bonds that replace proline with another N-substituted amino acid are also likely to adopt the cis isomer.

<span class="mw-page-title-main">Carboxypeptidase</span>

A carboxypeptidase is a protease enzyme that hydrolyzes (cleaves) a peptide bond at the carboxy-terminal (C-terminal) end of a protein or peptide. This is in contrast to an aminopeptidases, which cleave peptide bonds at the N-terminus of proteins. Humans, animals, bacteria and plants contain several types of carboxypeptidases that have diverse functions ranging from catabolism to protein maturation. At least two mechanisms have been discussed.

In molecular biology, immunophilins are endogenous cytosolic peptidyl-prolyl isomerases (PPI) that catalyze the interconversion between the cis and trans isomers of peptide bonds containing the amino acid proline (Pro). They are chaperone molecules that generally assist in the proper folding of diverse "client" proteins. Immunophilins are traditionally classified into two families that differ in sequence and biochemical characteristics. These two families are: "cyclosporin-binding cyclophilins (CyPs)" and "FK506-binding proteins (FKBPs)". In 2005, a group of dual-family immunophilins (DFI) has been discovered, mostly in unicellular organisms; these DFIs are natural chimera of CyP and FKBPs, fused in either order.

<span class="mw-page-title-main">Beta hairpin</span>

The beta hairpin is a simple protein structural motif involving two beta strands that look like a hairpin. The motif consists of two strands that are adjacent in primary structure, oriented in an antiparallel direction, and linked by a short loop of two to five amino acids. Beta hairpins can occur in isolation or as part of a series of hydrogen bonded strands that collectively comprise a beta sheet.

<span class="mw-page-title-main">Prolyl isomerase</span> Enzyme

Prolyl isomerase is an enzyme found in both prokaryotes and eukaryotes that interconverts the cis and trans isomers of peptide bonds with the amino acid proline. Proline has an unusually conformationally restrained peptide bond due to its cyclic structure with its side chain bonded to its secondary amine nitrogen. Most amino acids have a strong energetic preference for the trans peptide bond conformation due to steric hindrance, but proline's unusual structure stabilizes the cis form so that both isomers are populated under biologically relevant conditions. Proteins with prolyl isomerase activity include cyclophilin, FKBPs, and parvulin, although larger proteins can also contain prolyl isomerase domains.

<span class="mw-page-title-main">Parvulin</span>

Parvulin, a 92-amino acid protein discovered in E. coli in 1994, is the smallest known protein with prolyl isomerase activity, which catalyzes the cis-trans isomerization of proline peptide bonds. Although parvulin has no homology with larger prolyl isomerases such as cyclophilin and FKBP, it does share structural features with subdomains of other proteins involved in preparing secreted proteins for export from the cell.

<span class="mw-page-title-main">Antamanide</span> Chemical compound

Antamanide is a cyclic decapeptide isolated from a fungus, the death cap: Amanita phalloides. It is being studied as a potential anti-toxin against the effects of phalloidin and for its potential for treating edema. It contains 1 valine residue, 4 proline residues, 1 alanine residue, and 4 phenylalanine residues with a structure of c(Val-Pro-Pro-Ala-Phe-Phe-Pro-Pro-Phe-Phe). It was isolated by determining the source of the anti-phalloidin activity from a lipophillic extraction from the organism. It has been shown that antamanide can react to form alkali metal ion complexes. These include complexes with sodium and calcium ions. When these complexes are formed, the cyclopeptide structure undergoes a conformational change.

<span class="mw-page-title-main">Aldehyde dehydrogenase 18 family, member A1</span> Protein-coding gene in the species Homo sapiens

Delta-1-pyrroline-5-carboxylate synthetase (P5CS) is an enzyme that in humans is encoded by the ALDH18A1 gene. This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. As reported by Bruno Reversade and colleagues, ALDH18A1 deficiency or dominant-negative mutations in P5CS in humans causes a progeroid disease known as De Barsy Syndrome.

β turns are the most common form of turns—a type of non-regular secondary structure in proteins that cause a change in direction of the polypeptide chain. They are very common motifs in proteins and polypeptides. Each consists of four amino acid residues. They can be defined in two ways:

  1. By the possession of an intra-main-chain hydrogen bond between the CO of residue i and the NH of residue i+3;
  2. By having a distance of less than 7Å between the Cα atoms of residues i and i+3.

In epigenetics, proline isomerization is the effect that cis-trans isomerization of the amino acid proline has on the regulation of gene expression. Similar to aspartic acid, the amino acid proline has the rare property of being able to occupy both cis and trans isomers of its prolyl peptide bonds with ease. Peptidyl-prolyl isomerase, or PPIase, is an enzyme very commonly associated with proline isomerization due to their ability to catalyze the isomerization of prolines. PPIases are present in three types: cyclophilins, FK507-binding proteins, and the parvulins. PPIase enzymes catalyze the transition of proline between cis and trans isomers and are essential to the numerous biological functions controlled and affected by prolyl isomerization Without PPIases, prolyl peptide bonds will slowly switch between cis and trans isomers, a process that can lock proteins in a nonnative structure that can affect render the protein temporarily ineffective. Although this switch can occur on its own, PPIases are responsible for most isomerization of prolyl peptide bonds. The specific amino acid that precedes the prolyl peptide bond also can have an effect on which conformation the bond assumes. For instance, when an aromatic amino acid is bonded to a proline the bond is more favorable to the cis conformation. Cyclophilin A uses an "electrostatic handle" to pull proline into cis and trans formations. Most of these biological functions are affected by the isomerization of proline when one isomer interacts differently than the other, commonly causing an activation/deactivation relationship. As an amino acid, proline is present in many proteins. This aids in the multitude of effects that isomerization of proline can have in different biological mechanisms and functions.


  1. "Proline". PubChem. U.S. National Library of Medicine. Archived from the original on 16 January 2014. Retrieved 8 May 2018.
  2. Belitz HD, Grosch W, Schieberle P (2009-01-15). Food Chemistry. p. 15. ISBN   978-3-540-69933-0. Archived from the original on 2016-05-15.
  3. Nelson DL, Cox MM. Principles of Biochemistry. New York: W.H. Freeman and Company.
  4. "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 9 October 2008. Retrieved 5 March 2018.
  5. Plimmer RH (1912) [1908], Plimmer RH, Hopkins FG (eds.), The chemical composition of the proteins, Monographs on biochemistry, vol. Part I. Analysis (2nd ed.), London: Longmans, Green and Co., p. 130, retrieved September 20, 2010
  6. "Proline". Amino Acids Guide. Archived from the original on 2015-11-27.
  7. "Proline". American Heritage Dictionary of the English Language, 4th edition. Archived from the original on 2015-09-15. Retrieved 2015-12-06.
  8. Lehninger AL, Nelson DL, Cox MM (2000). Principles of Biochemistry (3rd ed.). New York: W. H. Freeman. ISBN   1-57259-153-6..
  9. 1 2 Ion Channel Factsbook: Extracellular Ligand-Gated Channels. Academic Press. 16 November 1995. p. 126. ISBN   978-0-08-053519-7. Archived from the original on 26 April 2016.
  10. 1 2 Henzi V, Reichling DB, Helm SW, MacDermott AB (April 1992). "L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons". Molecular Pharmacology. 41 (4): 793–801. PMID   1349155.
  11. 1 2 Arslan OE (7 August 2014). Neuroanatomical Basis of Clinical Neurology (Second ed.). CRC Press. p. 309. ISBN   978-1-4398-4833-3. Archived from the original on 14 May 2016.
  12. Verbruggen N, Hermans C (November 2008). "Proline accumulation in plants: a review". Amino Acids. 35 (4): 753–759. doi:10.1007/s00726-008-0061-6. PMID   18379856. S2CID   21788988.
  13. Shrestha A, Fendel A, Nguyen TH, Adebabay A, Kullik AS, Benndorf J, et al. (September 2022). "Natural diversity uncovers P5CS1 regulation and its role in drought stress tolerance and yield sustainability in barley". Plant, Cell & Environment. 45 (12): 3523–3536. doi:10.1111/pce.14445. PMID   36130879. S2CID   252438394.
  14. Shrestha A, Cudjoe DK, Kamruzzaman M, Siddique S, Fiorani F, Léon J, Naz AA (June 2021). "Abscisic acid-responsive element binding transcription factors contribute to proline synthesis and stress adaptation in Arabidopsis". Journal of Plant Physiology. 261: 153414. doi:10.1016/j.jplph.2021.153414. PMID   33895677. S2CID   233397785.
  15. Muzammil S, Shrestha A, Dadshani S, Pillen K, Siddique S, Léon J, Naz AA (October 2018). "An Ancestral Allele of Pyrroline-5-carboxylate synthase1 Promotes Proline Accumulation and Drought Adaptation in Cultivated Barley". Plant Physiology. 178 (2): 771–782. doi:10.1104/pp.18.00169. PMC   6181029 . PMID   30131422.
  16. Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, Martin M, de la Vega-Correa L, Zapata C, et al. (May 2022). "Microbiota alterations in proline metabolism impact depression". Cell Metabolism. 34 (5): 681–701.e10. doi: 10.1016/j.cmet.2022.04.001 . hdl:10230/53513. PMID   35508109. S2CID   248528026.
  17. Pavlov MY, Watts RE, Tan Z, Cornish VW, Ehrenberg M, Forster AC (January 2009). "Slow peptide bond formation by proline and other N-alkylamino acids in translation". Proceedings of the National Academy of Sciences of the United States of America. 106 (1): 50–54. Bibcode:2009PNAS..106...50P. doi: 10.1073/pnas.0809211106 . PMC   2629218 . PMID   19104062..
  18. Buskirk AR, Green R (January 2013). "Biochemistry. Getting past polyproline pauses". Science. 339 (6115): 38–39. Bibcode:2013Sci...339...38B. doi:10.1126/science.1233338. PMC   3955122 . PMID   23288527.
  19. Morris AL, MacArthur MW, Hutchinson EG, Thornton JM (April 1992). "Stereochemical quality of protein structure coordinates". Proteins. 12 (4): 345–364. doi:10.1002/prot.340120407. PMID   1579569. S2CID   940786.
  20. Szpak P (2011). "Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis". Journal of Archaeological Science . 38 (12): 3358–3372. doi:10.1016/j.jas.2011.07.022. Archived from the original on 2012-01-18.
  21. Alderson TR, Lee JH, Charlier C, Ying J, Bax A (January 2018). "Propensity for cis-Proline Formation in Unfolded Proteins". ChemBioChem. 19 (1): 37–42. doi:10.1002/cbic.201700548. PMC   5977977 . PMID   29064600.
  22. Sarkar SK, Young PE, Sullivan CE, Torchia DA (August 1984). "Detection of cis and trans X–Pro peptide bonds in proteins by 13C NMR: application to collagen". Proceedings of the National Academy of Sciences of the United States of America. 81 (15): 4800–4803. Bibcode:1984PNAS...81.4800S. doi: 10.1073/pnas.81.15.4800 . PMC   391578 . PMID   6589627.
  23. Thomas KM, Naduthambi D, Zondlo NJ (February 2006). "Electronic control of amide cistrans isomerism via the aromatic-prolyl interaction". Journal of the American Chemical Society. 128 (7): 2216–2217. doi:10.1021/ja057901y. PMID   16478167.
  24. Gustafson CL, Parsley NC, Asimgil H, Lee HW, Ahlbach C, Michael AK, et al. (May 2017). "A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates Circadian Rhythms". Molecular Cell. 66 (4): 447–457.e7. doi:10.1016/j.molcel.2017.04.011. PMC   5484534 . PMID   28506462.
  25. Siebert KJ. "Haze and Foam". Cornell AgriTech. Archived from the original on 2010-07-11. Retrieved 2010-07-13. Accessed July 12, 2010.
  26. Pazuki A, Asghari J, Sohani MM, Pessarakli M, Aflaki F (2015). "Effects of Some Organic Nitrogen Sources and Antibiotics on Callus Growth of Indica Rice Cultivars". Journal of Plant Nutrition. 38 (8): 1231–1240. doi:10.1080/01904167.2014.983118. S2CID   84495391.
  27. Vogel, Practical Organic Chemistry 5th edition

Further reading