Peptide-mediated targeting of hepatocytes via low density lipoprotein receptor-related protein (LRP)

Ludtke, James J.; Sokoloff, Alex V.; Wong, So C.; Strickland, Dudley K.; Wolff, Jon A.

doi:10.1080/10717540902975000

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…As reported 33 , P17 peptide targeted multiple cargos including proteins, siRNA, and DNA-liposome complex to hepatocytes by interaction with the receptor LRP on cell surface, leading to endocytosis of cargos by hepatocytes. Indeed, P17-tagged G12-scFv was taken up by primary mouse hepatocytes more efficiently than untagged G2-scFv, as observed by immunofluorescence confocal microscopy (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 76%

“…The P17 protein from the tail of T7 phage can target phage particles yet also other cargos including small molecules, proteins, siRNA, DNA polyplexes, and liposomes to hepatocytes in vitro and in vivo 31 , 32 . This is predominantly mediated by the association of a 33-amino acid (aa) P17 protein segment (named P17 peptide or P17 tag hereafter) with cell-surface low density lipoprotein receptor-related protein (LRP) 33 . We previously generated an scFv of mAb G12 18 , 34 , which targets the surface protein of hepatitis B virus (HBV), a virus with pronounced liver tropism.…”

Section: Introductionmentioning

confidence: 99%

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A 33-residue peptide tag increases solubility and stability of Escherichia coli produced single-chain antibody fragments

et al. 2022

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Single-chain variable fragments (scFvs), composed of variable domains of heavy and light chains of an antibody joined by a linker, share antigen binding capacity with their parental antibody. Due to intrinsically low solubility and stability, only two Escherichia coli-produced scFvs have been approved for therapy. Here we report that a 33-residue peptide, termed P17 tag, increases the solubility of multiple scFvs produced in Escherichia coli SHuffle strain by up to 11.6 fold. Hydrophilic sequence, especially charged residues, but not the predicted α-helical secondary structure of P17 tag, contribute to the solubility enhancement. Notably, the P17 tag elevates the thermostability of scFv as efficiently as intra-domain disulfide bonds. Moreover, a P17-tagged scFv targeting hepatitis B virus surface proteins shows over two-fold higher antigen-binding affinity and virus-neutralizing activity than the untagged version. These data strongly suggest a type I intramolecular chaperone-like activity of the P17 tag. Hence, the P17 tag could benefit the research, production, and application of scFv.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

A 33-residue peptide tag increases solubility and stability of Escherichia coli produced single-chain antibody fragments

et al. 2022

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“…New possibilities for abrogating the tumor‐promoting and metabolic adaptative functions of CSC through LRP targeting may ultimately be envisioned. In fact the identification of LRP as a cognate receptor for a peptide sequence of T7 phage protein p17 offers a new ligand–receptor combination for cell delivery of therapeutic agents 31. A new neurotherapeutic platform based on the Angiopep‐2 peptide, a sequence derived from ligands that bind to LRP‐1 located at the BBB, demonstrated efficient transport across the BBB into brain parenchyma 5, 32, 33.…”

Section: Discussionmentioning

confidence: 99%

Members of the low‐density lipoprotein receptor‐related proteins provide a differential molecular signature between parental and CD133(+) DAOY medulloblastoma cells

Annabi

Doumit

Plouffe

et al. 2010

Molecular Carcinogenesis

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Members of the low-density lipoprotein receptor-related protein (LRP) family are involved in metabolic stress and resistance phenotypes of cancer cells. New breakthroughs in brain cancer therapy have exploited that molecular signature and proved that efficient delivery of therapeutic agents involve LRP-mediated mechanisms. We performed gene expression profiling of CD133, a cell surface cancer stem cell marker, and of LRP in response to in vitro nutrient deprivation. We found that CD133 was selectively induced in serum-starved DAOY medulloblastoma cells but not in U87MG glioblastoma cells. Such CD133 induction was correlated to increases in LRP-1 and LRP-1b gene and protein expression. When a specific CD133(+) DAOY cell population was sorted from parental DAOY, we found increases in LRP-5 and LRP-8. Uptake of alpha(2)-macroglobulin, a specific LRP-1/1b ligand, was increased in serum-starved parental DAOY cells but not in CD133(+) DAOY cells, and receptor-associated protein (RAP), which binds to all cell surface LRPs, was able to compete for that uptake. Conversely, RAP binding was increased in serum-starved parental DAOY but alpha(2)-macroglobulin was unable to compete for such uptake. Strategies aiming at targeting cancer stem cell metabolic adaptative responses, such as that through LRP differential expression within the brain tissue microenvironmental niche, can now be envisioned.

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In vivo phage display — A discovery tool in molecular biomedicine

Bábíčková

Tóthová

Boor

et al. 2013

Biotechnology Advances

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Peptide-mediated targeting of hepatocytes via low density lipoprotein receptor-related protein (LRP)

Cited by 5 publications

References 28 publications

A 33-residue peptide tag increases solubility and stability of Escherichia coli produced single-chain antibody fragments

A 33-residue peptide tag increases solubility and stability of Escherichia coli produced single-chain antibody fragments

Members of the low‐density lipoprotein receptor‐related proteins provide a differential molecular signature between parental and CD133(+) DAOY medulloblastoma cells

In vivo phage display — A discovery tool in molecular biomedicine

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