Evidence map›Paper›PMID 27829783›Full record

ArticleMolecular vision2016

Peptide redesign for inhibition of the complement system: Targeting age-related macular degeneration.

Rohith R Mohan, Andrea P Cabrera, Reed E S Harrison, Ronald D Gorham, Lincoln V Johnson, Kaustabh Ghosh, Dimitrios Morikis

Open access · greenAbstract read
PubMed Full text at PMC
In one paragraph

Article in Molecular vision, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Rohith R MohanDepartment of Bioengineering, University of California, Riverside, CA.
Andrea P CabreraDepartment of Bioengineering, University of California, Riverside, CA.
Reed E S HarrisonDepartment of Bioengineering, University of California, Riverside, CA.
Ronald D GorhamDepartment of Bioengineering, University of California, Riverside, CA.
Lincoln V JohnsonCenter for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara, CA.
Kaustabh GhoshDepartment of Bioengineering, University of California, Riverside, CA.
Dimitrios MorikisDepartment of Bioengineering, University of California, Riverside, CA.
University of California, Riverside · USUniversity of California, Santa Barbara · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTo redesign a complement-inhibiting peptide with the potential to become a therapeutic for dry and wet age-related macular degeneration (AMD).

methodsWe present a new potent peptide (Peptide 2) of the compstatin family. The peptide is developed by rational design, based on a mechanistic binding hypothesis, and structural and physicochemical properties derived from molecular dynamics (MD) simulation. The inhibitory activity, efficacy, and solubility of Peptide 2 are evaluated using a hemolytic assay, a human RPE cell-based assay, and ultraviolet (UV) absorption properties, respectively, and compared to the respective properties of its parent peptide (Peptide 1).

resultsThe sequence of Peptide 2 contains an arginine-serine N-terminal extension (a characteristic of parent Peptide 1) and a novel 8-polyethylene glycol (PEG) block C-terminal extension. Peptide 2 has significantly improved aqueous solubility compared to Peptide 1 and comparable complement inhibitory activity. In addition, Peptide 2 is more efficacious in inhibiting complement activation in a cell-based model that mimics the pathobiology of dry AMD.

conclusionsWe have designed a new peptide analog of compstatin that combines N-terminal polar amino acid extensions and C-terminal PEGylation extensions. This peptide demonstrates significantly improved aqueous solubility and complement inhibitory efficacy, compared to the parent peptide. The new peptide overcomes the aggregation limitation for clinical translation of previous compstatin analogs and is a candidate to become a therapeutic for the treatment of AMD.

Indexed as

Amino Acid SequenceAnimalsCell LineComplement System ProteinsHemolysisHumansInhibitory Concentration 50Macular DegenerationPeptidesPeptides, CyclicRabbitsSolubilityComplement System ProteinscompstatinPeptidesPeptides, Cyclic

Identifiers

PMID27829783
PMCPMC5082644
OpenAlexW2564158673

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.