Peptides can be particularly difficult to modify due to their propensity for low aqueous solubility. Depending on the sequence, the peptide may only be soluble at high or low pH (due to acidic or basic residues.) Additionally, some residues such as A, F, L, V, are very hydrophobic at any pH. Since the S-4FB will modify all lysines present (as well as the N-terminus), it may be possible that the peptide is being over-modified with 4FB. Thermo Scientific offers some tips for working with troublesome sequences. Ultimately, it may be necessary to either optimize the sequence by substituting hydrophilic residues or by putting the HyNic on the peptide during SPPS. You can also change the strategy by putting the more hydrophilic HyNic on the peptide and the 4FB on the protein – but beware – it is easy to over-modify proteins with 4FB and they, too, will precipitate. I would shoot for 2-3 4FB molecules per mol of 50 KDa protein (ie., add 5 equivalents to the crude reaction with the protein at ~3 mg/mL.)