The Role of 4-phosphonodifluoromethyl- and 4-phosphono-phenylalanine in the selectivity and cellular uptake of SH2 domain ligands

Incorporation of 4-phosphonodifluoromethyl-phenylalanine (F2Pmp) and 4-phosphono-phenylalanine into SH2 targeted peptides and peptidomimetic ligands was found to effect binding affinity and selectivity of these ligands toward the Src and Abl SH2 domains. Furthermore, dipeptide analogs containing these phosphonate amino acids were used to produce prodrugs with excellent cellular delivery and reconversion rates.