title: Structural evaluation of a novel pro-apoptotic peptide coupled to CNGRC tumor homing sequence by NMR.
abstract: 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.
authors.affiliation: Chemistry Department, University of San Diego, San Diego, CA 92110, USA.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Sandoval
authors.forename: Bernhard H
authors.initials: BH
authors.lastname: Geierstanger
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujimura
authors.forename: Calvin
authors.initials: C
authors.lastname: Balatbat
authors.forename: Taylor
authors.initials: T
authors.lastname: Williams
authors.forename: Julio
authors.initials: J
authors.lastname: de Unamuno
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Whiles-Lillig
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ellerby
authors.forename: H Michael
authors.initials: HM
authors.lastname: Ellerby
authors.forename: Patricia
authors.initials: P
authors.lastname: Jennings
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Plesniak
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation
chemical_list: D008823:Micelles; D009842:Oligopeptides