Protecting groups

Hi Szilard,

We are carrying out peptide reactions with reactor. A question that we have is:

Is there a way to specify that we only want to couple the last amino acid in the peptide with another amino acid (i.e. protection, deprotection)? We would like to be able to use the same reaction scheme for alpha, beta2 and beta3 amino acids, if possible. BTW we are using the reactor component in pipeline pilot. Thanks sor that!

Best

Hi,

Is this question related to your other one I answered few days ago? Could you use the general alpha amino acid reaction scheme I added there? Or was anything wrong with it?

Best regards,

Gyuri

The scheme that you gave to us last time was completely
fine. Thanks for that. The problem we have now is that when we add each amino
acid when building a peptide we would like for them to add only at the last
residue and not at any of the others. I have made reaction schemes using your advice
last time but when I couple the amino acids reactions are taking place at
inappropriate places in the peptide. E.g. the 4^th residue in the
chain should only join to the 3^rd but it is also joining to the 1^st.
This is because the scheme just says that a reaction should take place when the
functional group is recognised but is does not specify that this shouldn’t occur
anywhere apart from the last peptide. We were wondering if there is a way to
specify this in reactor/pipeline pilot?

 

I hope that makes sense! Any help would be much appreciated.

 

Best

For better understanding, can you please show one or more problematic cases as example? The reaction you get and the one you would expect. Images will do.

A specific problem that we have is as follows:

We couple an alpha amino acid with a beta3. Then we want to couple another alpha AA to these residues at the beta3 side, using our reaction scheme for beta3 + alpha. In PP there are 125 products when the first 2 are coupled and we would expect this number to stay the same throughout the chain. However, when the 3rd residue is added we get 216 products. I had a look at the products and it seems that the 3rd AA is being coupled with the 1st alpha AA as well as the beta3. I think this is because our reaction scheme just indicates that an alpha AA OH group should join to an NH when the NH is in the format of a beta3 AA (I've attached a copy of this scheme). So when this pattern is found the alpha AA will couple, even if it is joining at the wrong place in the chain.

Do you know if there is a way to specify in reactor or PP that we only want the next AA to couple with last AA?

Yes, you can surely define that reaction
selectively in Reactor.

Thank you for the attached file. The reaction scheme seems to have few issues that might influence the results. One thing is, that the leaving hydrogen of your amino group is not displayed explicitly, that can lead to valence problems. Furthermore, it might be a problem, that it is just a nitrogen and not specifically an amino nitrogen, so might match an amide nitrogen as well. Please do not forget, that the reactant of your generic reaction scheme are substructure queries, so the unfilled valences of the atoms can be substituted in the matching input molecules.

I would like to help, but I am not sure that I understand the specific case clearly. Seeing the images of the input reactants of the problematic step, the expected products,
and the received
products might help.

Included are reactants 1 and 2 and products A and B. Product A is what we want but we are getting product A and product B. Reactant 2 is coupling with reactant 1 at two places but we just want it to couple at the last amino acid.

I've attached product B to next message because I couldnt fit all 4...

product B

Thank you for the files and the images. Are you sure that reactant1 is correct? I can see only one amino acid in that molecule. The other side does not seem an amino acid.

If that is correct, then the reaction seems to be a decarboxylation and water elimination.

Please try the reaction scheme below:
[H:5][O:4][C:2](=[O:3])[N:1]C=O.[H:8][O:7][C:6](=O)C[#7]>>[#7]C[C:6](=O)[N:1]C=O

I mapped all of the atoms that are disappearing or having changing bonds. You can paste it in Marvin, or if you want you can run the reaction from the command line as well:

react -r alpha_beta3X-1.mrv reactant1.mol reactant2.mol

Is it the transformation you are looking for?

Hi Gyuri
Thanks so much for your help so far. So I think the main issue here is that we need to be able to react alpha-amino acids, B2/B3- homoamino acids sequentially as in a normal peptide condensation rxn.
What is really key is that we need to be able to specify that the rxn must only take place at the last amino acid and none of the others on the growing peptide.


Your replies so far have really helped us iron out issues to date!

I have included an example of exactly the type of thing we try to do.

Thanks again

Andy

 

You probably just need to be able to specify that an amino acid can be alpha ot beta. Please find attached a modified version of the original peptideformation reaction in MRV format containing link nodes specifying that the number of carbons between the carboxyl and amino groups can be 1 or 2.

Since the reaction follows the scheme, the carboxyl group of the first reactant will react with the amino group of the second reactant. So if you always feed back the resulting peptide as the first reactant in the next step, it will grow further on its carboxyl end.

That works great Gyuri

Best

Andy

Hi Gyuri

Sorry to bother you. That works fine for the first coupling reaction but to react a dipeptide with another alpha/beta amino acid this doesn't work. Any help greatly appreciated,

Best

Andy

Can you please attach the problematic dipeptide and the amino acid to couple or send them to me in a mail?

Yeah sure. Here you go. This was just an example of reactants that did not work but I suppose it would be the same for all of them. The test file was reactant 1 and the Phe was reactant 2.

Cheers.

Oh, yes. The SMARTS part of the scheme specified that the nitrogen should be amine, not amide. But this is not necessary for the first reactant containing the reacting carboxyl functionality. Please see the attached reaction file and compare it to the previous one to understand what I changed.