Talk:Peptide synthesis

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Wiki Education Foundation-supported course assignment[edit]

This article is or was the subject of a Wiki Education Foundation-supported course assignment. Further details are available on the course page. Student editor(s): Mboyajian.

Above undated message substituted from Template:Dashboard.wikiedu.org assignment by PrimeBOT (talk) 06:22, 17 January 2022 (UTC)[reply]

Taken from Fmoc/Boc SPPS comparison section[edit]

This is not sourced and also vague/irrelevant, potentially misleading and/or factually incorrect in parts. I don't know what the table adds (at least without more detail/clarification) Algertzars (talk) 07:53, 8 January 2018 (UTC)[reply]

Comparison of t-Boc and Fmoc solid-phase peptide synthesis[edit]

Both the Fmoc and Boc methods offer advantages and disadvantages. The selection of one technique over another is thus made on a case-by-case basis.[1]

Boc Fmoc
Requires special equipment Yes No
Cost of reagents Lower Higher
Solubility of peptides Higher Lower
Purity of hydrophobic peptides High May be lower
Problems with aggregation Less frequently More frequently
Synthesis time ~20 min/amino acid ~20–60 min/amino acid
Cleavage from resin HF TFA
Safety Potentially dangerous Relatively safe
Orthogonal No Yes

Boc SPPS uses special equipment to handle the final cleavage and deprotection step, which requires anhydrous hydrogen fluoride. Because the final cleavage of the peptide with Fmoc SPPS uses TFA, this special equipment is not necessary. The solubility of peptides generated by Boc SPPS is generally higher than those generated with the Fmoc method, because fluoride salts are higher in solubility than TFA salts. Next, problems with aggregation are generally more of an issue with Fmoc SPPS, primarily because the removal of a Boc group with TFA yields a positively charged α-amino group, whereas the removal of an Fmoc group yields a neutral α-amino group. The electrostatic repulsion of the positively charged α-amino group limits the formation of secondary structure on the resin. Finally, the Fmoc method is considered orthogonal, since α-amino group deprotection is with base, while final cleavage from the resin is with acid. The Boc method utilizes acid for both deprotection and cleavage from the resin. Hence, both methods possess advantages and disadvantages for their application in specific situations, and several factors must be considered to decide between the methods.

Unsourced or badly sourced[edit]

moved this here as it is all unsourced or badly sourced:

Solid-phase synthesis

Since its introduction over 40 years ago, SPPS has been significantly optimized. First, the resins themselves have been optimized.[2][non-primary source needed] Furthermore, the 'linkers' between the C-terminal amino acid and polystyrene resin have improved attachment and cleavage to the point of mostly quantitative yields.[3][4][5][non-primary source needed] The evolution of side chain protecting groups has limited the frequency of unwanted side reactions. In addition, the evolution of new activating groups on the carboxyl group of the incoming amino acid have improved coupling and decreased epimerization. Finally, the process itself has been optimized. In Merrifield's initial report, the deprotection of the α-amino group resulted in the formation of a peptide-resin salt, which required neutralization with base prior to coupling. The time between neutralization of the amino group and coupling of the next amino acid allowed for aggregation of peptides, primarily through the formation of secondary structures, and adversely affected coupling. The Kent group reported that concomitant neutralization of the α-amino group and coupling of the next amino acid led to improved coupling.[6] Each of these improvements has helped SPPS become the robust technique that it is today.[according to whom?]

There are two majorly used forms of SPPS – Fmoc and Boc. Unlike ribosome protein synthesis, solid-phase peptide synthesis proceeds in a C-terminal to N-terminal fashion. The N-termini of amino acid monomers is protected by either of these two groups and added onto a deprotected amino acid chain. Automated synthesizers are available for both techniques, though many research groups continue to perform SPPS manually.

Solid-phase synthesis

The name solid support implies that reactions are carried out on the surface of the support, but this is not the case. Reactions also occur within these particles, and thus the term "solid support" better describes the insolubility of the polymer. The physical properties of the solid support, and the applications to which it can be utilized, vary with the material from which the support is constructed, the amount of cross-linking, as well as the linker and handle being used. Most scientists in the field believe that supports should have the minimum amount of cross-linking to confer stability. This should result in a well-solvated system where solid-phase peptide synthesis can be carried out.

References

  1. ^ Nilsson BL, Soellner MB, Raines RT (2005). "Chemical synthesis of proteins". Annual Review of Biophysics and Biomolecular Structure. 34: 91–118. doi:10.1146/annurev.biophys.34.040204.144700. PMC 2845543. PMID 15869385.
  2. ^ Mitchell, A. R. K., S.B.H.; Engelhard, M.; Merrifield, R.B. (1978). "A new synthetic route to tert-butyloxycarbonylaminoacyl-4-(oxymethyl)phenylacetamidomethyl-resin, an improved support for solid-phase peptide synthesis". J. Org. Chem. 43 (13): 2845–2852. doi:10.1021/jo00408a022. {{cite journal}}: Unknown parameter |lastauthoramp= ignored (|name-list-style= suggested) (help)CS1 maint: multiple names: authors list (link)
  3. ^ Wang, S.-S. (1973). "p-alkoxybenzyl alcohol resin and p-alkoxybenzyloxycarbonylhydrazide resin for solid phase synthesis of protected peptide fragments". J. Am. Chem. Soc. 95 (4): 1328–33. doi:10.1021/ja00785a052. PMID 4687686.
  4. ^ Matsueda, G. R. a. S., J.M. (1981). "A p-methylbenzylhydrlamine resin for improved solid-phase synthesis of peptide amides". Peptides. 2 (1): 45–50. doi:10.1016/S0196-9781(81)80010-1. PMID 7243625.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Sieber, P. (1987). "A new acid-labile anchor group for the solid-phase synthesis of C-terminal peptide amides by the Fmoc method". Tetrahedron Lett. 28: 2107–10. doi:10.1016/S0040-4039(00)96055-6.
  6. ^ Schnolzer, M. A., P.; Jones, A.; Alewood, D.; Kent, S.B.H. (2007). "In Situ Neutralization in Boc-chemistry Solid Phase Peptide Synthesis". Int. J. Peptide Res. Therap. 13 (1–2): 31–44. doi:10.1007/s10989-006-9059-7.{{cite journal}}: CS1 maint: multiple names: authors list (link)

-- Jytdog (talk) 02:54, 7 January 2018 (UTC)[reply]

I'm trying to clean up this article, I just wrote most of the below as a more concise summary and am trying to cut out waffle. Can we not try and find sources rather than just removing it? Algertzars (talk) 03:35, 7 January 2018 (UTC)[reply]
Actually your edits were exacerbating the problems the tags described. You did not add any sources in your edits. We love experts in Wikipedia but this article has become truly terrible from people just writing what they know instead of editing Wikipedia - which means finding reliable sources, summarizing them, and citing them. Would you please have a read of WP:EXPERT and follow the advice there? I do appreciate your desire to improve this article, but adding yet more unsourced WP:OR is not what it needs...Jytdog (talk) 03:39, 7 January 2018 (UTC)[reply]
I'm not just writing everything I know - I'm trying to give a concise overview and can add citations. This is very basic material and is covered in most of the text books already cited. It would be more constructive to add citation needed than just remove it. The article is a mess because there is so much badly organized and irrelevant information. I was trying to remedy that broadly first. Algertzars (talk) 03:45, 7 January 2018 (UTC)[reply]
OK, I will revert back to where you were, and let's see what you can do! Jytdog (talk) 04:36, 7 January 2018 (UTC)[reply]
Thanks. I'd appreciate you put <citation needed> where you can if there are any more problems - I'm trying to salvage as much of what is already there as I can (even though there is a large amount of unreferenced material). As I mentioned much of it can be referenced using standard text books, but this will take some time. — Preceding unsigned comment added by Algertzars (talk • contribs) 05:36, 7 January 2018 (UTC)[reply]
Removed content from here that was transferred back into the main article Algertzars (talk) 04:29, 8 January 2018 (UTC)[reply]

Microwave refs[edit]

I agree that this chunk, removed by User:Smokefoot, was poor. Mostly uncited, except for two seemingly cherry-picked primary-ref examples to cite specific claims. However, here are some secondary refs to support that the general topic is of value:

  • Pedersen, Søren L.; Tofteng, A. Pernille; Malik, Leila; Jensen, Knud J. (2012). "Microwave heating in solid-phase peptide synthesis". Chem. Soc. Rev. 41: 1826–1844. doi:10.1039/C1CS15214A.
  • Kappe, C. Oliver; Stadler, Alexander; Dallinger, Doris (2012). Microwaves in Organic and Medicinal Chemistry. Methods and Principles in Medicinal Chemistry. Vol. 52 (Second ed.). Wiley. ISBN 9783527331857. — several comments about the presence of microwave reactors in many automated synthesizers

On the other hand, one of the primary-cited claims about reduced racemization really does need to go (not even a side comment of a key valuable aspect), because there is dispute in the primaries (e.g., doi:10.1021/jo8013897). DMacks (talk) 14:34, 3 September 2018 (UTC)[reply]

@DMacks: Will do. Thanks for your help.
One other thing is that I finally figured out that the article is almost exclusively about solid phase synthesis, vs solution methods. Maybe solution methods are completely kaput but for di- and tripeptides possibly not.--Smokefoot (talk) 14:39, 3 September 2018 (UTC)[reply]

--Smokefoot (talk) 14:39, 3 September 2018 (UTC)[reply]

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