Intramolecular lactame bridge (Asp-Lys)

[adrianandreica]

Is that somebody who did a peptide with intramolecular lactame bridge.
What coupling reagent (HCTU, HATU) is more suitable for the cyclization reaction.
What's the yieald of the cyclization reaction?

Thank you guys.

[AplaGen]

Dear adrianandreica,

as nearly all in peptide synthesis the answer is sequence depending. Do you want to do the cyclization on resin or in solution.

To my experience cyclizations on resin do not work well and you get many side-products - although I have a lot of literature concerning that approach. On resin I always got low yields (max. 5%). The best reagent in my approaches was Pybop - but as mentioned that is sequence depending. If you have a sterical problem HATU might be better.

In case of cyclizations in solution you have in principle one big advantage: you could purify the peptide before cyclization. This approach is of course only suitable if you do not have too many other functional side chain groups (perfect if you have only one acid and one amine). In solution it is of course extremely important to have a highly diluted solution of peptide and a high reagent concentration. In this case I would not recommend HATU (might deactivate the amine compound) but Pybop ... that kind of reaction in solution is highly "pH"-depending, so you will have to optimize the amount of base needed. The yields for cyclizations in solution in my past experiments was about 20-25%. That sounds higher than the on-resin-approach, but I purified the linear peptide by HPLC before so the overall-yield was of course lower. It depends on the impurity profil which approach is the best for you.

Without knowing the sequence it is hard to give you more tips.

Good luck!

AplaGen