[opsomath]

Due to some practical lab issues, I have to change the solvent conditions for a reaction between a PEG-amine and an amino acid NHS ester that I do a lot. Currently I run it in 10 mM PBS, pH 7.2 - I am thinking of moving to a similar buffer solution but one which contains about 1-5% acetonitrile. Do y'all foresee any problems with this?

[Doc Oc]

I did a lot of peptide couplings in organic solvents.  Any reason you're using aqueous buffers?  Is one of the components insoluble in organic solvent?  DMF works wonders (although getting rid of it is a bit of a pain).

[Honclbrif]

My advice in these matters is usually "If it works, it works. Don't mess with success".

However, if change is unavoidable, a few % ACN in there probably won't ruin things. If you're adding it to improve solubility, it can probably only improve matters too. EDC coupling is pretty robust and I've seen ACN recommended as a solvent for these reactions before.

[BobfromNC]

ACN should not bother a amide coupling in aqueous conditions.   I would be more careful with DMF to make sure that it is a new or good bottle, as traces of dimethylamine would do more harm than anything else.  THF can also work.