Uptake of branched polypeptides with poly[L-Lys] backbone by bone-marrow culture-derived murine macrophages? The role of the class A scavenger receptor

Rita Szabó, Leanne Peiser, Annette Plüddemann, Szilvia Bösze, Sigrid Heinsbroek, Siamon Gordon, Ferenc Hudecz

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15 Citations (Scopus)


Selective delivery of antiparasitic or antibacterial drugs into infected macrophages could be a promising approach for improved therapies. Methotrexate conjugate with branched chain polypeptides exhibited pronounced anti-Leishmania activity in vitro and in vivo as reported here earlier. To identify structural requirements for efficient uptake of branched polypeptides, we have studied murine bone marrow culture-derived macrophages (BMMφ) from 129/ICR mice. We report on the translocation characteristics of structurally closely related compounds labeled with 5(6)-carboxyfluorescein. We found that this process is dependent on experimental conditions (e.g. polypeptide concentration, incubation time, and temperature). Using specific inhibitors as well as macrophages from wild-type and class-A scavenger receptor knockout (SR-A -/-) mice, we demonstrated that SR-A was involved in the endocytosis of some polypeptides depending on their charge. Uptake could be blocked by unlabeled polypeptide, by SR-A inhibitors, and by specific anti-SR-A monoclonal antibody. The polyanionic polypeptide poly[Lys(Succ-Glu1.0-DL-Ala3.8)] (SuccEAK) with high charge density translocated more efficiently than poly[Lys(Ac-Glu 1.0-DL-Ala3.8)] (AcEAK), which had a lower anionic charge density. On the basis of experimental data presented, SuccEAK can be considered as a potential candidate for the design of a macromolecular carrier for specific drug delivery of bioactive entities into macrophages via SR-A.

Original languageEnglish
Pages (from-to)1442-1450
Number of pages9
JournalBioconjugate Chemistry
Issue number6
Publication statusPublished - Nov 1 2005


ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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