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Structural Evaluation of a Novel Pro‐apoptotic Peptide Coupled to CNGRC Tumor Homing Sequence by NMR
Author(s) -
Sandoval Cristina M.,
Geierstanger Bernhard H.,
Fujimura Satoshi,
Balatbat Calvin,
Williams Taylor,
De Unamuno Julio,
WhilesLillig Jennifer A.,
Ellerby Lisa M.,
Michael Ellerby H.,
Jennings Patricia,
Plesniak Leigh A.
Publication year - 2006
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2006.00394.x
Subject(s) - peptide , homing (biology) , peptide sequence , vesicle , sequence (biology) , chemistry , apoptosis , micelle , microbiology and biotechnology , biophysics , biochemistry , biology , membrane , ecology , aqueous solution , gene
Hunter‐killer peptides (HKPs) are synthetic peptides that target specific cell types for apoptosis. These studies report functional and structural characteristics of HKP9, an hunter‐killer peptide that specifically targets tumor vasculature with a new apoptotic sequence. Vesicle leakage experiments were performed as a model for membrane perturbing activity. Placement of the homing sequence reduces both cell toxicity and vesicle leakage activity. NMR studies elucidate the conformation and orientation of HKP9 in micelles. The positively charged end of the HKP9 killing sequence is solvent exposed; however, the central portion of the peptide is helical and buried in dodecylphosphorylcholine micelles. The homing sequence is less solvent exposed than in a previously reported tumor‐homing peptide. The results suggest that solvent accessibility of the homing sequence should be considered in design of future peptides.