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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
38
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pubmed:dateCreated |
2009-10-6
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pubmed:abstractText |
Screening of phage libraries expressing random peptides for binding to prostate cancer cells primarily yielded peptides that had a C-terminal arginine (or rarely lysine) residue, usually in a consensus context R/KXXR/K. Phage expressing these sequences and synthetic nanoparticles coated with them bound to and were internalized into cells. The C-terminal arginine (or lysine) was essential to the activity; adding another amino acid, or even blocking the free carboxyl group of this arginine residue by amidation, eliminated the binding and internalizing activity. An internal R/KXXR/K can be exposed and switched on by a cleavage by a protease. The strict requirement for C-terminal exposure of the motif prompted us to term the phenomenon the C-end rule (CendR). Affinity chromatography showed that the CendR peptides bind to neuropilin-1 (NRP-1) on the target cells. NRP-1 is a cell-surface receptor that plays an essential role in angiogenesis, regulation of vascular permeability, and the development of the nervous system. VEGF-A165 and other ligands of NRP-1 possess a C-terminal CendR sequence that interacts with the b1 domain of NRP-1 and causes cellular internalization and vascular leakage. Our CendR peptides have similar effects, particularly when made multivalent through coupling to a particle. We also noted a unique and important activity of these peptides: penetration and transportation through tissues. The peptides were able to take payloads up to the nanoparticle size scale deep into extravascular tissue. Our observations have implications in drug delivery and penetration of tissue barriers and tumors.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-11259444,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-11327725,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-11425332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-11849958,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-11891274,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-12032302,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-12053175,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-12639809,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-12643747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-12778165,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-14667505,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-15601762,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-15920019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-16328161,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-16371354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-16513643,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-1672046,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-16959272,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-17405859,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-17503412,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-17600129,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-17699853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-17983687,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-18180379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-18391792,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-18522648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-2447074,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-2735925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-2849509,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-2849510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-6823562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-8915183,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-9008163,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805273-9529250
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16157-62
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
pubmed-meshheading:19805273-Humans,
pubmed-meshheading:19805273-Animals,
pubmed-meshheading:19805273-Mice,
pubmed-meshheading:19805273-Lung,
pubmed-meshheading:19805273-Prostatic Neoplasms,
pubmed-meshheading:19805273-Peptides,
pubmed-meshheading:19805273-Arginine,
pubmed-meshheading:19805273-Peptide Fragments,
pubmed-meshheading:19805273-Male,
pubmed-meshheading:19805273-Neoplasm Transplantation,
pubmed-meshheading:19805273-Amino Acid Sequence,
pubmed-meshheading:19805273-Protein Binding,
pubmed-meshheading:19805273-Tissue Distribution,
pubmed-meshheading:19805273-Transplantation, Heterologous,
pubmed-meshheading:19805273-Binding Sites,
pubmed-meshheading:19805273-Mice, Inbred BALB C,
pubmed-meshheading:19805273-Binding, Competitive,
pubmed-meshheading:19805273-Cell Line, Tumor,
pubmed-meshheading:19805273-Mice, Nude,
pubmed-meshheading:19805273-Chromatography, Affinity,
pubmed-meshheading:19805273-Endocytosis,
pubmed-meshheading:19805273-Transfection,
pubmed-meshheading:19805273-Vascular Endothelial Growth Factor A,
pubmed-meshheading:19805273-Microscopy, Confocal,
pubmed-meshheading:19805273-Neuropilin-1,
pubmed-meshheading:19805273-Peptide Library
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