[Nescafe]

Hi,

I was wondering if anyone here has had to do peptide coupling in water. My material is really polar to a point that it partially dissolves in DMSO. It only readily dissolves in solvents capable of hydrogen bonding such as MeOH or Water.

So I was wondering has anyone tried peptide coupling in water or is it an insane thing to do?

Thanks,

Nescafe.

[Irlanur]

I'm not an organic chemist, but theres the KAHA or Bode-Coupling. but that's usually done do synthesize big proteins/Peptides from smaller peptides.

[BobfromNC]

EDC has been used to do amide couplings in aqueous solvents.   Water is better than methanol, as it will not form the ester.   But NMP and DMF are also fine solvents for couplings if DMSO does not work.    You will need a larger excess of the coupling agents.   You could also try making a pentafluorophenol ester of the acid, it can react with amines in water.   There are many know methods, but all are more difficult than normal methods, and usually are only practical for one or two amide couplings. 

[TheUnassuming]

You can certainly do EDC coupling in water.  It was the go-to for bioconjugation of proteins for a time. 
I think you will get increased levels of the N-acylurea formation, which isn't optimal... but at least you will get product!
As Bob said, use a large excess of EDC.