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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Weerakkody, Dhammika Moshnikova, Valentina Engelman, Donald M. Andreev, Oleg A. Thakur, Mak S. Moshnikova, Anna Daniels, Jennifer Reshetnyak, Yana K. |
| Description | Author Affiliation: Weerakkody D ( Physics Department, University of Rhode Island, Kingston, RI 02881, USA.); |
| Abstract | Cancer is a complex disease with a range of genetic and biochemical markers within and among tumors, but a general tumor characteristic is extracellular acidity, which is associated with tumor growth and development. Acidosis could be a universal marker for cancer imaging and the delivery of therapeutic molecules, but its promise as a cancer biomarker has not been fully realized in the clinic. We have discovered a unique approach for the targeting of acidic tissue using the pH-sensitive folding and transmembrane insertion of pH (low) insertion peptide (pHLIP). The essence of the molecular mechanism has been elucidated, but the principles of design need to be understood for optimal clinical applications. Here, we report on a library of 16 rationally designed pHLIP variants. We show how the tuning of the biophysical properties of peptide-lipid bilayer interactions alters tumor targeting, distribution in organs, and blood clearance. Lead compounds for PET/single photon emission computed tomography and fluorescence imaging/MRI were identified, and targeting specificity was shown by use of noninserting variants. Finally, we present our current understanding of the main principles of pHLIP design. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 15 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Membrane Proteins Chemistry Neoplasms Pathology Peptides Amino Acid Sequence Animals Cell Membrane Metabolism Green Fluorescent Proteins HeLa Cells Hydrogen-Ion Concentration Lipid Bilayers Magnetic Resonance Imaging Mice Mice, Nude Microscopy, Fluorescence Molecular Sequence Data Neoplasm Transplantation Protein Folding Thermodynamics Tomography, Emission-Computed, Single-Photon Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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