Stepwise synthesis of oligonucleotide-peptide conjugates containing guanidinium and lipophilic groups in their 3 '-termini

作者：Grijalvo Santiago; Terrazas Montserrat; Avino Anna; Eritja Ramon^*

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(7): 2144-2147.

DOI：10.1016/j.bmcl.2010.02.049

• ODN-peptide conjugates
• Dickerson-Drew dodecamer
• Luciferase
• Postsynthetic guanidinylation reaction
• Ureas
• Antisense oligonucleotide
• Phosphorothioates

Two different series of oligonucleotide-peptide conjugates have been efficiently synthesized by stepwise solid-phase synthesis. First, oligonucleotides and oligonucleotide phosphorothioates containing polar groups at the 3'-termini, such as amine and guanidinium groups were prepared. ODNs conjugates carrying several lysine residues were obtained directly from Fmoc deprotection whereas ODN conjugates with guanidinium groups were obtained by post-synthetic guanidinylation. The second family contains different urea moieties that were achieved by standard protocols. All products were fully characterized by reversed phase HPLC and MALDI-TOF mass spectrometry yielding satisfactory results. Oligonucleotide-phosphorothioate conjugates were evaluated as potential antisense oligonucleotides in the inhibition of the luciferase gene.

• 出版日期2010-4-1