RNA POLYMERASE II CARBOXYL TERMINAL DOMAIN-DERIVED PEPTIDES

摘要

The targeting molecules described herein are derived from the RNA polymerase II carboxyl terminus, consisting of at least two to three hexapeptide repeats of the structure: YX1PX2X3PX4, where Y is tyrosine, P is proline, X can be any amino acid, and X1, X2 and X3 are most preferably serine or threonine, covalently conjugated to a bioactive molecule, most preferably an oligonucleotide, preferably via a linker consisting of one to two amino acids or a carbon chain of equivalent length attached using amide or disulfide chemistry to the tyrosine at the N-terminus of the peptide, leaving a free carboxyl. The peptide can be phosphorylated to alter the association with certain molecules in the nucleus, such as proteins having a serine/arginine motif and Sm snRNPs. For example, it is demonstrated that phosphorylated CTD-derived peptides bind to these nuclear proteins associated with transcription and splicing.