prenylated

Prenylated refers to a molecule that has undergone prenylation, a biochemical modification in which isoprenoid units are covalently attached. The most common prenyl groups are farnesyl (a 15-carbon chain) and geranylgeranyl (a 20-carbon chain). Prenylation can occur on proteins or small organic molecules and often increases hydrophobicity, affecting localization, stability, and interactions.

In proteins, prenylation typically targets those with a C-terminal CaaX motif (C = cysteine, a = aliphatic amino acids, X = one of several residues). Farnesyltransferase attaches a farnesyl group, while geranylgeranyltransferases attach a geranylgeranyl group. After attachment, the CaaX motif is often proteolyzed and carboxylmethylated; some proteins may also undergo further palmitoylation. This processing helps anchor proteins to membranes and modulates signal transduction. Many small GTPases, such as members of the Ras and Rho families, rely on prenylation for proper localization and function. Because these pathways influence cell growth and differentiation, prenylation has been investigated as a drug target, notably via farnesyltransferase inhibitors in cancer research, though results have varied.

In secondary metabolism, prenylation is performed by prenyltransferases that attach prenyl groups to aromatic substrates, producing prenylated flavonoids, coumarins, stilbenes, and related compounds. Such modifications can alter cellular localization, bioavailability, and biological activity, often enhancing interactions with membranes or protein targets. Prenylated compounds are found across plants and microbes and contribute to diversity in natural products and pharmacologically relevant molecules.