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dc.contributor.author Plesniak, Leigh A. en
dc.contributor.author Parducho, Jonathan I. en
dc.contributor.author Ziebart, Angie en
dc.contributor.author Geierstanger, Bernhard H en
dc.contributor.author Whiles-Lillig, Jennifer en
dc.contributor.author Melacini, Guiseppe en
dc.contributor.author Jennings, Patricia A. en
dc.date.accessioned 2012-07-31T16:49:47Z en
dc.date.available 2012-07-31T16:49:47Z en
dc.date.issued 2004 en
dc.identifier.citation Plesniak, L., Parducho, J., Ziebart, A. Geierstanger, B., Whiles, J., Melacini, G., and Jennings. P. "Orientation and helical conformation of a tissue-specific hunter-killer peptide in micelles." Protein Science 13, 1988-1996 (2004). en
dc.identifier.uri http://hdl.handle.net/10211.1/1511 en
dc.description Published by and copyright by The Protein Society. en
dc.description.abstract Hunter-killer peptides are chimeric synthetic peptides that selectively target specific cell types for an apoptotic death. These peptides, which are models for potential therapeutics, contain a homing sequence for receptor-mediated interactions and a pro-apoptotic sequence. Homing domains have been designed to target angiogenic tumor cells, prostate cells, arthritic tissue and, most recently, adipose tissue. After a receptor-mediated internalization, the apoptotic sequence, which contains D-enantiomer amino acids, initiates apoptosis through mitochondrial membrane disruption. We have begun structure and functional studies on a peptide (HKP1) that specifically targets angiogenic tumor cells for apoptosis. As a model for mitochondrial membrane disruption, we have examined peptide-induced leakage of a calcein fluorophore from large unilamellar vesicles. These experiments demonstrate more potent leakage activity by HKP1 than the peptide lacking the homing domain. Circular dichroism and 2D homonuclear NMR experiments demonstrate that this tumor-specific HKP adopts a left-handed amphipathic helix in association with dodecylphosphorylcholine micelles in a parallel orientation to the lipid–water interface with the homing domain remaining exposed to solvent. The amphipathic helix of the apoptotic domain orients with nonpolar leucine and alanine residues inserting most deeply into the lipid environment. en
dc.description.sponsorship This work was supported by grants from the UCSD Cancer Center (CCTPJEN-33645G), the NIH (R15 GM068431-01), and a Cotrell College Science Award from Research Corporation (CC5657). en
dc.language.iso en_US en
dc.publisher Protein Science en
dc.subject apoptosis en
dc.subject nuclear magnetic resonance en
dc.subject circular dichroism en
dc.subject peptide en
dc.title Orientation and Helical Conformation of a Tissue-specific Hunter-killer Peptide in Micelles en
dc.type Article en
dc.relation.journal Protein Science en
dc.contributor.sonomaauthor Whiles-Lillig, Jennifer en


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