Nanoparticle/peptide method of blocking potassium channels
Inventors
Delehanty, James B. • Muroski, Megan • Oh, Eunkeu • Deschamps, Jeffrey R.
Assignees
US Department of Navy • RB Distribution Inc
Publication Number
US-11878064-B2
Publication Date
2024-01-23
Expiration Date
2040-09-10
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Abstract
A nanoparticle (NP)-peptide conjugate provides efficient steric hindrance/blockage of cellular membrane potassium (K+) channels to mediate depolarization of cellular membrane potential.
Core Innovation
The invention provides a nanoparticle (NP)-peptide conjugate that efficiently blocks cellular membrane potassium (K+) channels by steric hindrance, mediating depolarization of the cellular membrane potential. Specifically, the conjugate uses a gold nanoparticle (AuNP) covalently bound to a modified tertiapin peptide (TPN-Q) to enhance potassium channel blocking activity compared to the free peptide.
The background problem is that existing potassium channel blockers, such as dalfampridine, dofetilide, and amiodarone, tend to be nonspecific, exhibit a range of binding affinities and off-target effects, and often bind irreversibly. There is a clear need for new potassium channel blockers that can provide improved activity and potentially reversible effects.
The innovation addresses this need by conjugating a stabilized peptide derivative, TPN-Q, to gold nanoparticles using click chemistry. This conjugation enhances the stability and functionality of the peptide, augments its channel-blocking activity by 2- to 3-fold, and enables faster and more efficient depolarization of neuronal-like differentiated PC-12 cells compared to the free peptide. The spacers appended to the peptide decrease steric hindrance, allowing effective interaction with the potassium channel.
Claims Coverage
The patent contains one independent method claim focused on blocking potassium channels using a specific nanoparticle-peptide conjugate construct.
A method of blocking potassium channels using a gold nanoparticle-peptide conjugate
The method comprises providing a construct that includes a gold nanoparticle conjugated to a peptide comprising SEQ ID NO: 1 together with a spacer sequence, and contacting mammalian cells with this construct to block potassium channels on the cells.
The claim defines a method leveraging a nanoparticle conjugated stabilized peptide to selectively block potassium channels on mammalian cells, emphasizing the conjugation construct and its application for channel blockage.
Stated Advantages
The AuNP-peptide conjugate enhances the biological activity of the TPN-Q peptide, improving potassium channel blocking compared to the free peptide.
The conjugate labeled with a dye can be easily tracked, enabling visualization of its binding to the plasma membrane.
Documented Applications
Nanoparticle-based therapeutics for activation of neurons and muscle cells through controlled modulation of membrane potential.
Non-invasive brain and muscle cell stimulation using controlled potassium channel blockage to modulate cellular membrane potential.
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