am9b10153_si_001.pdf (1.44 MB)
Coordination-Assisted Self-Assembled Polypeptide Nanogels to Selectively Combat Bacterial Infection
journal contribution
posted on 2019-09-03, 17:18 authored by Sudipta Panja, Rashmi Bharti, Goutam Dey, Nathaniel A. Lynd, Santanu ChattopadhyayIn
the present scenario, the invention of bacteria-selective antimicrobial
agent comprising negligible toxicity and hemolytic effect is a great
challenge. To surmount this challenge, here, a series of polypeptide
nanogels (PNGs) have been fabricated by a coordination-assisted self-assembly
of a mannose-conjugated antimicrobial polypeptide, poly(arginine-r-valine)-mannose (poly(Arg-r-Val)-M2), with Zn2+ ions. The fabricated PNGs are spherical
in shape with a unique structural appearance similar to that of Taxus baccata fruits. PNGs, with a unique structural
arrangement and threshold surface charge density, selectively interact
with the bacterial membrane and exhibit potent antimicrobial activity,
as reflected in their lower minimum inhibitory concentration values
(varies from 2 to 16 μg/mL). PNGs show a remarkably high binding
constant, 6.02 × 105 M–1 (from isothermal titration
calorimetry, ITC), with the bacterial membrane which manifests its
potent bactericidal effect. PNGs are nontoxic against mammalian and
red blood cells as reflected from their higher cell viability and
insignificant hemolytic effect. PNGs are taken up by the bacterial
membrane and selectively undergo structural deformation (scrutinized
by ITC) followed by an exposure of free poly(Arg-r-Val)-M2 molecules. The free poly(Arg-r-Val)-M2 molecules are enforced to lyse the bacterial
membrane (visualized by cryo-transmission electron microscopy) followed
by the diffusion of the cytoplasmic component out of the membrane
which culminates in the final death of the bacterium.
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ValSelectively Combatbacteria-selective antimicrobial agentcoordination-assisted self-assemblybactericidal effectthreshold surface charge densityconcentration valuesmembraneantimicrobial activitytitration calorimetrymannose-conjugated antimicrobial polypeptideblood cellsITCCoordination-Assisted Self-Assembled Polypeptide Nanogelscytoplasmic componentcell viabilityTaxus baccata fruitspolypeptide nanogelscryo-transmission electron microscopyPNG
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