O-MALONYLTYROSYL COMPOUNDS, O-MALONYLTYROSYL COMPOUND-CONTAINING PEPTIDES, AND USES THEREOF

摘要

The present invention relates to non-phosphorous containing O-malonyltyrosyl compounds of general formula (I), derivatives thereof, uses of the O-malonyltyrosyl compounds in the synthesis of peptides, and O-malonyltyrosyl compound-containing peptides. The O-malonyltyrosyl compounds and O-malonyltyrosyl compound-containing peptides of the present invention are uniquely stable to phosphatases, capable of crossing cell membranes, suitable for application to peptide synthesis of O-malonyltyrosyl compound-containing peptides, and amenable to prodrug derivatization for delivery into cells. The present invention also provides for O-malonyltyrosyl compound-containing peptides which exhibit inhibitory potency against binding interactions of receptor domains with phosphotyrosyl-containing peptide ligands. In formula (I), R1 and R2 are independently hydrogen, alkyl, aralkyl, alkaryl, aryl and heteroaryl; R3 is hydrogen, halogen, amino, hydroxy, and alkoxy; X is nitrogen or oxygen; R4 is hydrogen, alkyl, aralkyl, alkaryl, optionally substituted aryl, and heteroaryl; R5 is hydrogen, fluorenyl methoxy carbonyl (FMOC), tert-butoxy carbonyl (BOC), and carbobenzoxy (CBZ), carbamoyl, alkyl, amido, aryl, and heteroaryl; with the proviso that substituents of formula (I) which can be substituted are optionally substituted.