Artificial ion channel biosensor in human immunodeficiency virus gp41 drug sensing.
An ion channel biosensor is described for label-free detection of inhibitors which bind to the coiled coil domain of human immunodeficiency virus type 1 gp41. gp41 is the viral transmembrane glycoprotein responsible for fusion between HIV-1 and host cells. The N-terminal coiled coil domain binds three antiparallel C-heptad repeat peptides in the six helix bundle structure of trimeric gp41 that forms during fusion. Compounds able to prevent six-helix bundle formation by binding to the gp41 coiled coil could inhibit fusion and have important therapeutic potential. We have immobilized on gold a positively charged metallopeptide mimic of a section of the gp41 coiled coil containing a hydrophobic pocket suitable for small molecule binding. We demonstrate that the resulting sensor is able to transmit a current in the presence of negatively charged redox marker ions, therefore acting as an artificial ion channel. The electrochemical signal, measured by cyclic voltammetry, was modulated by specific analyte binding to the coiled coil. Nanomolar quantities of peptides and small molecules that bind in the hydrophobic pocket could be selectively detected, providing a method for label-free detection of binding to gp41.
Hou
Yanxia
Y
Department of Basic Sciences, Touro University-California, Vallejo, California 94592, USA.
Gochin
Miriam
M
D015374:Biosensing Techniques / Q000379:methods*; D016903:Drug Monitoring / Q000295:instrumentation*; D004563:Electrochemistry / Q000295:instrumentation / Q000379:methods; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors*; D023581:HIV Fusion Inhibitors / Q000032:analysis*; D006801:Humans; D007477:Ions; D018716:Molecular Mimicry; D010455:Peptides
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D007477:Ions; D010455:Peptides