Lactam reaction causes +85 MW side product

[p3ptideguy]

Hi all,

New to the forum here. I was wondering if anyone has experience in making lactam bonds using PyBOP/DIEA as the coupling agent? My labmates and I have been experiencing a +85/86 molecular weight side product when creating lactam bonds between residues such as a Glu-Ofm and Lys-Fmoc using a tBoc strategy for the ~30 residue peptide. The side product coelutes on reverse phase HPLC using water/ACN/TFA gradients, but can be seperated using ammonium bicarb buffers. It is clearly visible on mass spec and often cuts our lactam yields to under 50% as most of the reaction product is turned into this +85/86 entity. We have tried using 1-Hobt to supress the reaction but that does not work. I am not 100% sure but I also think I did one lactam under N2 and it might have supressed it, but I cannot remember entirely as it was months ago. Either way, we need help! Anyone have any suggestions? Same problem? Literature searches have not helped.....