Radiometal-labeled peptide-PNA conjugates for targeting bcl-2 expression: preparation, characterization, and in vitro mRNA binding

Bioconjug Chem. 2002 Nov-Dec;13(6):1176-80. doi: 10.1021/bc025591s.


A new antisense peptide-peptide nucleic acid (peptide-PNA) conjugate, designed for targeting bcl-2 expression, has been radiolabeled, characterized, and evaluated for bcl-2 mRNA binding in a cell-free system. A PNA complementary to the first six codons of the bcl-2 gene was synthesized by standard solid-phase Fmoc chemistry and conjugated to a new derivative of 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA) that allows macrocyclic radiometal chelates to be incorporated into any sequence position of a peptide-PNA conjugate. The DOTA-PNA conjugate was then coupled to a membrane-permeating transduction peptide, PTD-4, designed for intracellular delivery of the radiolabeled PNA. The conjugate was characterized by HPLC and ESI-MS and labeled with (111)In and (90)Y to high specific activities (>1000 Ci/mmol) with high radiochemical purity. Northern blot analysis showed that (90)Y-PTD-4-K(DOTA)-anti-bcl-2-PNA bound specifically to as little as 50 fmol of bcl-2 mRNA, a result equivalent to that obtained with the analogous (32)P-labeled DNA antisense oligonucleotide. Thus, the mRNA targeting properties of (111)In- and (90)Y-PTD-4-K(DOTA)-anti-bcl-2-PNA demonstrate potential for diagnostic imaging and targeted radiotherapy applications in bcl-2-positive cancers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Base Sequence
  • Drug Delivery Systems
  • Drug Design
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, bcl-2 / genetics*
  • Indium Radioisotopes
  • Peptide Nucleic Acids / chemical synthesis*
  • Peptide Nucleic Acids / genetics
  • Peptide Nucleic Acids / metabolism
  • Peptide Nucleic Acids / pharmacology*
  • Peptides / chemical synthesis*
  • Peptides / metabolism
  • Peptides / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Yttrium Radioisotopes


  • Antineoplastic Agents
  • Indium Radioisotopes
  • Peptide Nucleic Acids
  • Peptides
  • RNA, Messenger
  • Yttrium Radioisotopes