Hydrophilic

A hydrophilic molecule or residue is one that interacts well with water via hydrogen bonds or electrical charge. In a peptide, this property stems from charged side chains (aspartate, glutamate, lysine, arginine, histidine), from polar side chains (serine, threonine, asparagine, glutamine) and from the backbone amides, which act as hydrogen-bond donors and acceptors all the way along the chain.

Two consequences for research peptides

This one property accounts for the two most important practical traits of research peptides. They are generally simple to dissolve: a freeze-dried cake of a hydrophilic sequence dissolves in bacteriostatic water with light swirling and no co-solvent, which is why routine reconstitution suits most of the catalogue. They are, however, almost unable to cross membranes: the hydrogen-bonding capacity that makes water such a good solvent makes the lipid bilayer a poor one, which is the structural explanation for oral bioavailability close to zero and for the predominance of parenteral and mucosal routes.

Hydrophilicity shapes chromatography too: in reversed-phase HPLC, hydrophilic peptides come off early at low organic solvent levels, so the retention time on a certificate of analysis gives some rough indication of a sequence’s character. Very hydrophilic sequences also stick very little to plastic, which is convenient when preparing an aliquot.

Related terms

lipophilic · isoelectric point