Document Detail


Targeting heat shock proteins on cancer cells: selection, characterization, and cell-penetrating properties of a peptidic GRP78 ligand.
MedLine Citation:
PMID:  16878978     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Peptidic ligands can be used for specific cell targeting and the delivery of payloads into the target cell. Here we describe the screening of a pool of cyclic peptide phage display libraries using whole-cell panning against human melanoma cell line Me6652/4. This strategy resulted in the selection of the cyclic 13-mer Pep42, CTVALPGGYVRVC, which showed preferential internalization into melanoma cell line Me6652/4 versus the reference cell line Me6652/56. This translocation is a receptor-mediated process that does not require electrostatic interactions nor does it involve transfer to the lysosomal compartment. The cellular receptor for Pep42 was identified as the surface membrane form of glucose-regulated protein 78 (GRP78), a member of the heat shock protein family and a marker on malignant cancer cells. The cellular uptake and intracellular trafficking of Pep42-Quantum Dot conjugates was monitored by confocal laser microscopy, and colocalization within the endoplasmic reticulum was observed. The uptake of Pep42 could be blocked by a monoclonal antibody against the identified receptor. Furthermore, Pep42 was shown to target specifically GRP78-expressing cancer cells. The in vitro cytotoxicity of a Pep42-Taxol conjugate was evaluated by flow cytometry wherein the conjugate was shown to induce apoptosis and was more effective in promoting programmed cell death in Me6652/4 cells. In summary, the data presented suggest that cyclic peptide Pep42 might be a powerful tool in the construction of drug conjugates designed to selectively kill malignant cancer cells.
Authors:
Youngsoo Kim; Antonietta M Lillo; Sebastian C J Steiniger; Ying Liu; Carlo Ballatore; Andrea Anichini; Roberta Mortarini; Gunnar F Kaufmann; Bin Zhou; Brunhilde Felding-Habermann; Kim D Janda
Related Documents :
18229458 - Hsp70b' regulation and function.
9426298 - Pretreatment with hypertonic nacl protects mdck cells against high urea concentrations.
19224398 - The role of hsp27 and actin in the regulation of movement in human cancer cells respond...
9354938 - Effects of an inhibitor of protein kinases on the response to heat treatment in culture...
12829748 - Dynamic behavior of nuf2-hec1 complex that localizes to the centrosome and centromere a...
6310818 - Epstein-barr virus-induced precursor b cell lines from patients with congenital agammag...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemistry     Volume:  45     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-01     Completed Date:  2006-09-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9434-44     Citation Subset:  IM    
Affiliation:
The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Antibodies, Monoclonal / pharmacology
Antineoplastic Agents, Phytogenic / pharmacology
Cell Line, Tumor
Heat-Shock Proteins / drug effects,  genetics,  metabolism*
Humans
Ligands
Melanoma / chemistry,  metabolism*
Molecular Chaperones / drug effects,  genetics,  metabolism*
Molecular Sequence Data
Paclitaxel / pharmacology
Peptide Library
Peptides, Cyclic / drug effects,  genetics,  metabolism*
Protein Transport / drug effects
Grant Support
ID/Acronym/Agency:
A41986//PHS HHS; AI47127/AI/NIAID NIH HHS; CA112287/CA/NCI NIH HHS; HL63651/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antineoplastic Agents, Phytogenic; 0/Heat-Shock Proteins; 0/Ligands; 0/Molecular Chaperones; 0/Pep42 peptide; 0/Peptide Library; 0/Peptides, Cyclic; 0/molecular chaperone GRP78; 33069-62-4/Paclitaxel

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Contributions of basic amino acids in the autolysis loop of factor XIa to serpin specificity.
Next Document:  Selective alteration of the rate-limiting step in cytosolic aldehyde dehydrogenase through random mu...