Structural evaluation of a novel pro-apoptotic peptide coupled to CNGRC tumor homing sequence by NMR.
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.
Sandoval
Cristina M
CM
Chemistry Department, University of San Diego, San Diego, CA 92110, USA.
Geierstanger
Bernhard H
BH
Fujimura
Satoshi
S
Balatbat
Calvin
C
Williams
Taylor
T
de Unamuno
Julio
J
Whiles-Lillig
Jennifer A
JA
Ellerby
Lisa M
LM
Ellerby
H Michael
HM
Jennings
Patricia
P
Plesniak
Leigh A
LA
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
D008823:Micelles; D009842:Oligopeptides