proteinbinding

Protein binding is the reversible association of a ligand with a protein, yielding bound and free (unbound) fractions. In biology and pharmacology, the most studied case is plasma protein binding, where drugs and endogenous compounds bind to serum proteins such as albumin and alpha-1-acid glycoprotein. Binding is characterized by affinity (often expressed as the dissociation constant, Kd) and capacity (the number of binding sites), and it is typically saturable, following a binding isotherm.

For drugs, the unbound fraction (fu) is the pharmacologically active portion that can cross membranes, exert effects, be distributed to tissues, and be cleared by the kidney or liver. Bound drug acts as a reservoir that can release drug as free concentrations decline. High protein binding can prolong half-life and reduce tissue distribution, but can also lead to drug–drug interactions when two substances compete for the same binding sites.

Factors that influence protein binding include the concentration and composition of binding proteins (albumin, alpha-1-acid glycoprotein), drug properties such as lipophilicity and charge, pH, temperature, disease states, age, and co-administered drugs that displace bound ligands. Genetic variation in binding proteins can also affect binding.

Measurement of protein binding commonly uses equilibrium dialysis or ultrafiltration, sometimes coupled with mass spectrometry or HPLC. Interpreting protein binding requires distinguishing the bound and free fractions; total drug concentration alone can be misleading for highly bound compounds.

Protein binding is not limited to drugs; endogenous ligands such as hormones and metal ions also bind to proteins, influencing distribution and activity. In research and therapeutics, understanding binding is essential for pharmacokinetics, drug design, and assessment of potential interactions.