Tumor Cell Retention of Antibody Fab Fragments Is Enhanced by an Attached HIV TAT Protein-Derived Peptide

Anderson, Dave; Nichols, Everett J.; Manger, R; Woodle, D.; Barry, M. E.; Fritzberg, Alan R.

doi:10.1006/bbrc.1993.1903

Cited by 83 publications

(54 citation statements)

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“…As already discussed in a previous review [69], the coupling of cell specific antibodies to CPPs did increase their cellular internalization in vitro as expected [70]. However, it also reduced significantly their selectivity in vivo since non-targeted tissues took up the chimeric construct through non-specific internalization mediated by the CPP.…”

Section: Problems and Limitations Of Cpps For Drug Delivery In Vivosupporting

confidence: 72%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

310

272

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During the last decade, the potential of peptides for drug delivery into cells has been highlighted by the discovery of several cell-penetrating peptides (CPPs). CPPs are very efficient in delivering various molecules into cells. However, except in some specific cases, their lack of cell specificity remains the major drawback for their clinical development. At the same time, various peptides with specific binding activity for a given cell line (cell-targeting peptides) have also been reported in the literature. One of the goals of the next years will be to optimize the tissue and cell delivery of therapeutic molecules by means of peptides which combine both targeting and internalization advantages. In this review, we describe the main strategies that are currently in use or likely to be employed in the near future to associate both targeting and delivery properties.

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Section: Problems and Limitations Of Cpps For Drug Delivery In Vivosupporting

confidence: 72%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

310

272

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“…Single chain variable fragments (scFvs), antigen-binding fragments (Fab) and whole IgGs have been linked to several PTDs, including those derived from HIV1-TAT or Antennapedia protein ( Table 2). [139][140][141] As discussed, complex formation and the nature and size of particles are crucial transfection parameters. To reproduce optimal aggregation characteristics, particle sizes and zeta potentials of the protein/transfection reagent complexes have been monitored by electrophoretic light scattering.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Targeting antibodies to the cytoplasm

Marschall

Frenzel

Schirrmann

et al. 2011

mAbs

110

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“…Of particular interest for drug delivery is that exogenously added HIV-1 Tat efficiently crosses the plasma membranes of cells in an apparent energydependent fashion, localizes to the nucleus, and is functional, stimulating HIV-long terminal repeat-driven RNA synthesis (6)(7)(8)(9)(10)(11). The sequence responsible for the cellular uptake of HIV-1 Tat consists of the highly basic region, amino acid residues 49-57 (RKKRRQRRR) (12)(13)(14)(15)(16). The detailed mechanism for the cellular uptake of HIV-1 Tat 49 -57 remains unknown.…”

mentioning

confidence: 99%

The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters

Wender

Mitchell

Pattabiraman

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

1,485

1,446

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Certain proteins contain subunits that enable their active translocation across the plasma membrane into cells. In the specific case of HIV-1, this subunit is the basic domain Tat49-57 (RKKRRQRRR). To establish the optimal structural requirements for this translocation process, and thereby to develop improved molecular transporters that could deliver agents into cells, a series of analogues of Tat49-57 were prepared and their cellular uptake into Jurkat cells was determined by flow cytometry. All truncated and alaninesubstituted analogues exhibited diminished cellular uptake, suggesting that the cationic residues of Tat49-57 play a principal role in its uptake. Charge alone, however, is insufficient for transport as oligomers of several cationic amino acids (histidine, lysine, and ornithine) are less effective than Tat49-57 in cellular uptake. In contrast, a 9-mer of L-arginine (R9) was 20-fold more efficient than Tat49-57 at cellular uptake as determined by Michaelis-Menton kinetic analysis. The D-arginine oligomer (r9) exhibited an even greater uptake rate enhancement (>100-fold). Collectively, these studies suggest that the guanidinium groups of Tat49-57 play a greater role in facilitating cellular uptake than either charge or backbone structure. Based on this analysis, we designed and synthesized a class of polyguanidine peptoid derivatives. Remarkably, the subset of peptoid analogues containing a six-methylene spacer between the guanidine head group and backbone (N-hxg), exhibited significantly enhanced cellular uptake compared to Tat49-57 and even to r9. Overall, a transporter has been developed that is superior to Tat49-57, protease resistent, and more readily and economically prepared.

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Tumor Cell Retention of Antibody Fab Fragments Is Enhanced by an Attached HIV TAT Protein-Derived Peptide

Cited by 83 publications

References 0 publications

Cell-penetrating and cell-targeting peptides in drug delivery

Cell-penetrating and cell-targeting peptides in drug delivery

Targeting antibodies to the cytoplasm

The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters

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