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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: jestquim on February 06, 2020, 12:36:41 PM

Title: Chemical synthesis of a peptide
Post by: jestquim on February 06, 2020, 12:36:41 PM
I'd like to know how the next peptide could be prepared in a laboratory.
 
In several books, I've read that there are different ways to synthesize peptides: solution synthesis, solid phase synthesis, among others. But, when it comes to implementing one of the methods, I am not able. I hope you can help me.
Title: Re: Chemical synthesis of a peptide
Post by: Babcock_Hall on February 06, 2020, 02:15:40 PM
What have you found, so far?
Title: Re: Chemical synthesis of a peptide
Post by: jestquim on February 06, 2020, 02:18:49 PM
What have you found, so far?

So, for example, to form the Leu-Ala di-peptide, I would have to protect the Leu amino group and the alanine acid group. For example, it can be protected with benzyl chloroformate.
Title: Re: Chemical synthesis of a peptide
Post by: AWK on February 06, 2020, 02:47:00 PM
Wikipedia - peptide synthesis is a good start to this very comprehensive topic. Think about protecting the amino group of one amino acid and the carboxyl group of the other, and the coupling reagent.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564544/
Title: Re: Chemical synthesis of a peptide
Post by: rolnor on February 06, 2020, 06:07:54 PM
You can buy t-Butylesters of these amino acids with CBz-protected sidechain but they are not cheap I think. Final step would be hydrogenation. Its fun to work with solid phase but not neccesary in this case. Can you suggest in what end of the peptide you should start?
Title: Re: Chemical synthesis of a peptide
Post by: kriggy on February 07, 2020, 01:17:22 AM
You can buy t-Butylesters of these amino acids with CBz-protected sidechain but they are not cheap I think. Final step would be hydrogenation. Its fun to work with solid phase but not neccesary in this case. Can you suggest in what end of the peptide you should start?

While its not necessary, I would highly recommend. I tried making some dipeptides and it was pain.
Title: Re: Chemical synthesis of a peptide
Post by: jestquim on February 08, 2020, 05:17:33 AM
You can buy t-Butylesters of these amino acids with CBz-protected sidechain but they are not cheap I think. Final step would be hydrogenation. Its fun to work with solid phase but not neccesary in this case. Can you suggest in what end of the peptide you should start?

After reading it, I am still not able to make a synthesis of this peptide.
Title: Re: Chemical synthesis of a peptide
Post by: OrganicDan96 on February 08, 2020, 01:41:56 PM
You can buy t-Butylesters of these amino acids with CBz-protected sidechain but they are not cheap I think. Final step would be hydrogenation. Its fun to work with solid phase but not neccesary in this case. Can you suggest in what end of the peptide you should start?

While its not necessary, I would highly recommend. I tried making some dipeptides and it was pain.

i kew someone who used solid phase for  the synthesis of a simple dipeptide, it's much easier.
Title: Re: Chemical synthesis of a peptide
Post by: rolnor on February 08, 2020, 03:54:46 PM
You can buy t-Butylesters of these amino acids with CBz-protected sidechain but they are not cheap I think. Final step would be hydrogenation. Its fun to work with solid phase but not neccesary in this case. Can you suggest in what end of the peptide you should start?

After reading it, I am still not able to make a synthesis of this peptide.

You need to explain the thoughts you have, how would you start this synthesis, what startingmaterial would you use?
Title: Re: Chemical synthesis of a peptide
Post by: wildfyr on February 08, 2020, 05:57:35 PM
SPPS solid phase peptide synthesis using resins are the solution to this job.
Title: Re: Chemical synthesis of a peptide
Post by: jestquim on February 09, 2020, 02:53:07 PM
You can buy t-Butylesters of these amino acids with CBz-protected sidechain but they are not cheap I think. Final step would be hydrogenation. Its fun to work with solid phase but not neccesary in this case. Can you suggest in what end of the peptide you should start?

After reading it, I am still not able to make a synthesis of this peptide.

You need to explain the thoughts you have, how would you start this synthesis, what startingmaterial would you use?

I think that the best way is:
1. Protect the amino group of the amino acid leucine with the Fmoc group
2. Join the carbonyl end of the amino acid Leu to a reactive group of a resin.
3. Remove the protective group by treatment with a solution containing a weak organic base.
4. Protect the valine amino group with Fmoc. The amino acid is activated in its carboxyl group by DCC.
5. The amino group of leucine attacks the activated carboxyl group of valine to form a peptide bond.
6. We unprotect the Leu-Val di-peptide as in step 2. We add HF to hydrolyze the ester bond between the resin and the di-peptide.
7. Once we have the Leu-Val di-peptide, we protect the amino end with the Fmoc group, and proceed as before.
Title: Re: Chemical synthesis of a peptide
Post by: kriggy on February 10, 2020, 01:42:49 AM

I think that the best way is:
1. Protect the amino group of the amino acid leucine with the Fmoc group
2. Join the carbonyl end of the amino acid Leu to a reactive group of a resin.
3. Remove the protective group by treatment with a solution containing a weak organic base.
4. Protect the valine amino group with Fmoc. The amino acid is activated in its carboxyl group by DCC.
5. The amino group of leucine attacks the activated carboxyl group of valine to form a peptide bond.
6. We unprotect the Leu-Val di-peptide as in step 2. We add HF to hydrolyze the ester bond between the resin and the di-peptide.
7. Once we have the Leu-Val di-peptide, we protect the amino end with the Fmoc group, and proceed as before.


You are wasting time, you can buy fmoc-AAs commercialy for cheap money. While your idea might work its way too inefficient for this job:
a) you dont have to cleave the peptide from the resin only to attach it again
b) you will get even lower yields than normally
c) working with HF is not needed.

In SPS usually, the aminoacids are immobilized as esters to the resin and the you deprotect-acylate and repeate untill you get the peptide. You can start by immobilizing at N-terminus or even by side chain but its far less common.

Here is what I would do:

1) connect the fmoc-phenylalanine to wang resin using some set of obvious conditions (look it up, I think its DIC+dmap but im not 100%).
2) analyze the loading of the resin via cleaving the fmoc-AA from the resin and doing quantification
3) de-Fmoc with (20%) piperidine in DCM, should be super fast
4) make the peptide bond using another set of obvious conditions (DIC+HOBt or any other you wish)
5) repeat 3+4
6) cleave the peptide from resin using TFA:DCM cocktail and purify by HPLC
Title: Re: Chemical synthesis of a peptide
Post by: rolnor on February 10, 2020, 05:24:57 PM
If you dont have experience with solid phase peptide sunthesis I strongly suggest you make a litt. Search in scifinder, there is probably very similar or even exact peptides made, you will save a lot of time and money.