PEGylated polylysine peptides represent a new class of scavenger receptor inhibitors that may find utility at inhibiting DNA nanoparticle uptake by Kupffer cells in the liver. PEG-peptides inhibit scavenger receptors in the liver by a novel mechanism involving in situ formation of albumin nanoparticles. The present study developed a new in vivo assay used to explore the structure-activity-relationships of PEG-peptides to find potent scavenger receptor inhibitors. Radio-iodinated PEG-peptides were dosed i.v. in mice and shown to saturate liver uptake in a dose-dependent fashion. The inhibition potency (IC50) was dependent on both the length of a polylysine repeat and PEG molecular weight. PEG30kda-Cys-Tyr-Lys25 was confirmed to be a high molecular weight (33.5 kDa) scavenger receptor inhibitor with an IC50 of 18 μM. Incorporation of multiple Leu residues improved potency, allowing a decrease in PEG MW and Lys repeat, resulting in PEG5kda-Cys-Tyr-Lys-(Leu-Lys4)3-Leu-Lys that inhibited scavenger receptors with an IC50 = 20 μM. A further decrease in PEG MW to 2 kDa increased potency further, resulting in a low molecular weight (4403 g/mol) PEG-peptide with an IC50 of 3 μM. Optimized low molecular weight PEG-peptides also demonstrated potency when inhibiting the uptake of radio-iodinated DNA nanoparticles by the liver. This study demonstrates an approach to discover low molecular weight PEG-peptides that serve as potent scavenger receptor inhibitors to block nanoparticle uptake by the liver.
Pharmacology, Toxicology and Pharmaceutical Science
1
4%
Other
3
13%
Unknown
11
48%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 February 2023.
All research outputs
#11,322,103
of 34,089,221 outputs
Outputs from Molecular Pharmaceutics
#1,863
of 5,258 outputs
Outputs of similar age
#140,614
of 372,245 outputs
Outputs of similar age from Molecular Pharmaceutics
#42
of 144 outputs
Altmetric has tracked 34,089,221 research outputs across all sources so far. This one has received more attention than most of these and is in the 65th percentile.
So far Altmetric has tracked 5,258 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one has gotten more attention than average, scoring higher than 59% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 372,245 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.
We're also able to compare this research output to 144 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 59% of its contemporaries.
