Glossary
Lipophilic
Lipophilic means fat-loving: the molecule prefers a lipid phase over water. Why lipophilic residues promote aggregation and how they enable albumin binding.
A lipophilic molecule, or region of a molecule, preferentially moves into a lipid phase instead of water; the tendency is usually expressed as logP. In peptides it comes from particular side chains — phenylalanine, tryptophan, leucine, isoleucine, valine and methionine — and from any fatty acid or lipid tail that has been attached.
Three practical effects
The consequences are threefold. Solubility suffers: sequences with many lipophilic residues are reluctant to dissolve in plain aqueous buffer and may require a little organic co-solvent before dilution — a frequent reason why a vial seems to refuse to reconstitute. Aggregation increases: exposed lipophilic surfaces make peptides cluster together, giving turbidity or fibrils that no nominal purity value would warn you about. And lipophilicity can be engineered on purpose — the C18 fatty di-acid of semaglutide and the C16 chain of liraglutide are there to bind serum albumin and prolong half-life, the same goal that DAC and PEGylation reach by other means.
Lipophilicity and charge also work together: close to a peptide’s isoelectric point the net charge disappears and hydrophobic clustering takes over. The peptide solubility guide explains how to handle this in practice.
Related terms
hydrophilic · stability · methionine oxidation