Receptor Binding Affinity

Receptor binding affinity describes the strength of the non-covalent interaction between a ligand (such as a peptide) and its target receptor, quantified by the equilibrium dissociation constant (Kd), where a lower Kd indicates higher affinity. This parameter is fundamental to pharmacology because it determines how much of a compound is needed to occupy a meaningful fraction of receptors and produce a biological effect. Binding affinity is measured using techniques such as radioligand binding assays, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), and fluorescence polarisation. In peptide design, modifications to the amino acid sequence, cyclisation, and incorporation of non-natural amino acids can dramatically alter binding affinity and selectivity for target receptors. For example, Ipamorelin was engineered for high selectivity at the GHS-R1a receptor, resulting in growth hormone release without significant activation of cortisol or prolactin pathways, distinguishing it from less selective secretagogues like GHRP-6.