The anti-HIV pentameric pseudopeptide HB-19 is preferentially taken up in vivo by lymphoid organs where it forms a complex with nucleolin

The HB-19 pseudopeptide 5[K psi (CH2N)PR]-TASP, psi (CH2N) for reduced pept ide bond, is a specific inhibitor of HIV infection in different CD4(+) cell lines and in primary T-lymphocytes and macrophages. it blocks virus-partic le attachment to permissive cells by binding and forming a stable complex w ith nucleolin expressed on the cell surface. Here, we have investigated the tissue distribution of the tritiated HB-19 by using beta -radio imager who le-body mapping in rats. A rapid, selective, and stable distribution and ac cumulation of the systematically administered HB-19 was demonstrated within the spleen, liver, bone, and kidney as soon as 5 min following its adminis tration. No apparent uptake of HB-19 occurred in the brain and the muscle t issue. Interestingly and despite its rapid clearance from the blood, at 24 h postexposure a significant proportion of HB-19 was still recovered from t arget organs, of which 16-37% could be acounted for intact pseudopeptide. T he elimination of HB-19 mainly occurred by renal glomerular filtration and most of the excreted radioactivity appeared to be HB-19 metabolites. Finall y, injection of the biotin-labeled HB-19 pseudopeptide but not its control counterpart allowed the recovery of the HB-19-nucleolin complex from the li ver, spleen, thymus, and bone marrow, thus indicating that the in vivo mole cular target of HB-19 is surface nucleolin. our results demonstrate the pre ferential uptake and stability of HB-19 in lymphoid organs that are the sit e of HIV propagation.