ArticleJournal of medicinal chemistry2011
Structure-activity relationships in toll-like receptor 2-agonists leading to simplified monoacyl lipopeptides.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed.
- Peptide Antigen Modifications Influence the On-Target and Off-Target Antibody Response for an Influenza Subunit Vaccine.Vaccines · 2025Article
- Mono-Palmitoyl-N-Alkylurea Ligands as Specific Activators of Human Toll-Like Receptor 2/6 Heterodimer.Chembiochem : a European journal of chemical biology · 2024Article
- Fatty acids ofMicrobiology spectrum · 2024Article
- Chemical and Synthetic Biology Approaches for Cancer Vaccine Development.Molecules (Basel, Switzerland) · 2022Review
- Stereoisomeric PamRSC medicinal chemistry · 2022Article
- Lipopeptides for Vaccine Development.Bioconjugate chemistry · 2021Review
- Simplified Monopalmitoyl Toll-like Receptor 2 Ligand Mini-UPam for Self-Adjuvanting Neoantigen-Based Synthetic Cancer Vaccines.Chembiochem : a European journal of chemical biology · 2021Article
- Determining Whether Agonist Density or Agonist Number Is More Important for Immune Activation via Micoparticle Based Assay.Frontiers in immunology · 2020Article
- Development ofMolecules (Basel, Switzerland) · 2019Article
- Identification of Human Toll-like Receptor 2-Agonistic Activity in Dihydropyridine-Quinolone Carboxamides.ACS medicinal chemistry letters · 2019Article
- Targeting Cellular and Tissue HIV Reservoirs With Toll-Like Receptor Agonists.Frontiers in immunology · 2019Review
- Biomaterials for vaccine-based cancer immunotherapy.Journal of controlled release : official journal of the Controlled Release Society · 2018Review
- Diprovocims: A New and Exceptionally Potent Class of Toll-like Receptor Agonists.Journal of the American Chemical Society · 2018Article
- Dual TLR2 and TLR7 agonists as HIV latency-reversing agents.JCI insight · 2018Article
- Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.The AAPS journal · 2018Article
- An efficient and scalable synthesis of potent TLR2 agonistic PAMRSC advances · 2018Article
- TLR2 agonism reverses chemotherapy-induced neutropenia inBlood advances · 2017Article
- Peptide Lipidation - A Synthetic Strategy to Afford Peptide Based Therapeutics.Advances in experimental medicine and biology · 2017Review
- Position and length of fatty acids strongly affect receptor selectivity pattern of human pancreatic polypeptide analogues.ChemMedChem · 2014Article
- Determinants of activity at human Toll-like receptors 7 and 8: quantitative structure-activity relationship (QSAR) of diverse heterocyclic scaffolds.Journal of medicinal chemistry · 2014Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Toll-like receptor 2-agonistic lipopeptides typified by S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-R-cysteinyl-S-serine (PAM(2)CS) compounds are potential vaccine adjuvants. In continuation of previously reported structure-activity relationships on this chemotype, we have determined that at least one acyl group of optimal length (C(16)) and an appropriately oriented ester carbonyl group is essential for TLR2-agonistic activity. The spacing between one of the palmitoyl ester carbonyl and the thioether is crucial to allow for an important H-bond, which observed in the crystal structure of the lipopeptide:TLR2 complex; consequently, activity is lost in homologated compounds. Penicillamine-derived analogues are also inactive, likely due to unfavorable steric interactions with the carbonyl of Ser 12 in TLR2. The thioether in this chemotype can be replaced with a selenoether. Importantly, the thioglycerol motif can be dispensed with altogether and can be replaced with a thioethanol bridge. These results have led to a structurally simpler, synthetically more accessible, and water-soluble analogue possessing strong TLR2-agonistic activities in human blood.
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Registered trials
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.