Evidence map›Paper›PMID 26874401›Full record

ArticleBioorganic & medicinal chemistry letters2016

Synthesis of linear and cyclic peptide-PEG-lipids for stabilization and targeting of cationic liposome-DNA complexes.

Kai K Ewert, Venkata Ramana Kotamraju, Ramsey N Majzoub, Victoria M Steffes, Emily A Wonder, Tambet Teesalu, Erkki Ruoslahti, Cyrus R Safinya

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. 3D Columnar Phase of Stacked Short DNA Organized by Coherent Membrane Undulations.Langmuir : the ACS journal of surfaces and colloids · 2019
    Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. 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

8 authors at 3 institutions in 2 countries.

Kai K EwertDepartment of Materials, University of California, Santa Barbara, CA 93106, United States; Department of Physics, University of California, Santa Barbara, CA 93106, United States; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, United States. Electronic address: ewert@mrl.ucsb.edu.
Venkata Ramana KotamrajuCancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, United States.
Ramsey N MajzoubDepartment of Materials, University of California, Santa Barbara, CA 93106, United States; Department of Physics, University of California, Santa Barbara, CA 93106, United States; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, United States.
Victoria M SteffesDepartment of Materials, University of California, Santa Barbara, CA 93106, United States; Department of Physics, University of California, Santa Barbara, CA 93106, United States; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, United States; Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, United States.
Emily A WonderDepartment of Materials, University of California, Santa Barbara, CA 93106, United States; Department of Physics, University of California, Santa Barbara, CA 93106, United States; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, United States.
Tambet TeesaluCancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, United States; Center for Nanomedicine and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, United States; Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
Erkki RuoslahtiCancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, United States; Center for Nanomedicine and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, United States.
Cyrus R SafinyaDepartment of Materials, University of California, Santa Barbara, CA 93106, United States; Department of Physics, University of California, Santa Barbara, CA 93106, United States; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, United States. Electronic address: safinya@mrl.ucsb.edu.
University of California, Santa Barbara · USDiscovery Institute · USCancer Research Center · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
Structures of Lipid-DNA Nonviral Gene Delivery Systems 4R01GM059288 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI SAFINYA, CYRUS R · 1999 to 2016
$4.2M
Tumor Penetrating Peptides for Cancer TargetingR01CA152327 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RUOSLAHTI, ERKKI · 2011 to 2015
$2.0M
NCI NIH HHS CA152327NCI NIH HHS CA30199NCI NIH HHS P30 CA030199NCI NIH HHS R01 CA152327NIGMS NIH HHS GM-59288NIGMS NIH HHS R01 GM059288
6 · The paper itself

Abstract

Because nucleic acids (NAs) have immense potential value as therapeutics, the development of safe and effective synthetic NA vectors continues to attract much attention. In vivo applications of NA vectors require stabilized, nanometer-scale particles, but the commonly used approaches of steric stabilization with a polymer coat (e.g., PEGylation; PEG=poly(ethylene glycol)) interfere with attachment to cells, uptake, and endosomal escape. Conjugation of peptides to PEG-lipids can improve cell attachment and uptake for cationic liposome-DNA (CL-DNA) complexes. We present several synthetic approaches to peptide-PEG-lipids and discuss their merits and drawbacks. A lipid-PEG-amine building block served as the common key intermediate in all synthetic routes. Assembling the entire peptide-PEG-lipid by manual solid phase peptide synthesis (employing a lipid-PEG-carboxylic acid) allowed gram-scale synthesis but is mostly applicable to linear peptides connected via their N-terminus. Conjugation via thiol-maleimide or strain-promoted (copper-free) azide-alkyne cycloaddition chemistry is highly amenable to on-demand preparation of peptide-PEG-lipids, and the appropriate PEG-lipid precursors are available in a single chemical step from the lipid-PEG-amine building block. Azide-alkyne cycloaddition is especially suitable for disulfide-bridged peptides such as iRGD (cyclic CRGDKGPDC). Added at 10 mol% of a cationic/neutral lipid mixture, the peptide-PEG-lipids stabilize the size of CL-DNA complexes. They also affect cell attachment and uptake of nanoparticles in a peptide-dependent manner, thereby providing a platform for preparing stabilized, affinity-targeted CL-DNA nanoparticles.

Indexed as

CationsDNAHumansLipidsLiposomesMolecular StructureNanoparticlesPeptides, CyclicPolyethylene GlycolsCationsDNALipidsLiposomesPeptides, CyclicPolyethylene GlycolsHeterobifunctional poly(ethylene glycol)Homing peptidesLipid synthesisNanoparticlesNonviral gene deliveryPeptide–PEG–lipidsPoly(ethylene glycol)

Identifiers

PMID26874401
PMCPMC4775344
OpenAlexW2290215577

What OpenQuestion holds

Textmetadata
LicenceTDM
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.