Convergent solution-phase synthesis of a nucleopeptide using a protected oligonucleotide

A nucleopeptide was prepared in a convergent manner via segmental coupling of the protected biopolymers in solution. The resulting nucleopeptide (4b, 72%) containing the binding site of lambda repressor and a peptide containi ng the consensus sequence of the DNA binding helix of the helix turn-helix- proteins was obtained using only five equivalents of the peptide relative t o the oligonucleotide. This demonstrates that the recently developed method for the solution phase coupling of protected oligonucleotides is amenable to the convergent synthesis of larger nucleopeptides that are potentially c apable of adopting secondary structure. (C) 1999 Elsevier Science Ltd. All rights reserved.