Final answer:
Lysine methylation has different effects in the methyl-phosphate binary switch. N-terminal lysine methylation results in lower affinity but increased stability, while C-terminal methylation decreases affinity. Incorporation of an a-methyl amino acid reduces affinity but increases the half-life. The cis 3-phenylproline derivative in the N-terminal decreases affinity, but substitution in the C-terminal increases potency and half-life.
Step-by-step explanation:
Lysine methylation has different effects in the methyl-phosphate binary switch.
In the methylated series, lysine methylation at the N-terminal resulted in a 22-fold lower affinity and a 50 times increase in stability. C-terminal methylation was accompanied by a roughly 20-fold decrease in binding affinity without improvement in stability. Incorporation of an a-methyl amino acid reduced the binding affinity but increased the half-life. Additionally, when the cis 3-phenylproline derivative was incorporated into the N-terminal, the binding affinity decreased. However, replacement of the C-terminal phenylalanine by the cis 3-phenylproline moiety in the S,S,S configuration resulted in a more potent ligand with increased half-life.