Subtype selective binding properties of substituted linear melanocyte stimulating hormone analogues

The melanocortin receptors are peptide binding G-protein coupled receptors that play a role in important physiological functions such as energy balance, inflammatory processes and several aspects of reproduction. In this study, we synthesised 11 new linear MSH analogues and tested their binding to the human MC receptors (MC1, MC3, MC4 and MC5) expressed in COS cells. Our results show that introduction of Asp in position 4 similarly affects the binding to the MC1, MC4 and MC5 receptors, but drastically lowers the binding to the MC3 receptor. Arg(5) substitution shows relatively high affinity for the MC4 receptor, while the results also give further support for specific importance of His(6) f…