Studies on acid stability and solid-phase block synthesis of peptide–peptoid hybrids: ligands for formyl peptide receptors

Hansen, Anna Mette; Skovbakke, Sarah Line; Christensen, Simon Bendt; Perez-Gassol, Iris; Franzyk, Henrik

doi:10.1007/s00726-018-2656-x

Cited by 10 publications

(6 citation statements)

References 46 publications

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“…Peptidomimetics PM1 and PM2 were prepared by a solid-phase synthesis methodology involving assembly of dimeric and/or tetrameric building blocks on a Rink amide resin by using PyBOP as a coupling reagent as earlier reported ( 58 , 59 ). PMA (≥99% TLC), indomethacin (≥99% TLC), protease inhibitor cocktails, phosphatase inhibitor cocktails 2, and 10% neutral-buffered formalin solution were purchased from Sigma-Aldrich (St. Louis, MO, United States).…”

Section: Methodsmentioning

confidence: 99%

In vivo Anti-inflammatory Activity of Lipidated Peptidomimetics Pam-(Lys-βNspe)6-NH2 and Lau-(Lys-βNspe)6-NH2 Against PMA-Induced Acute Inflammation

Skovbakke

Masoudi

et al. 2020

Front. Immunol.

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Host Defense Peptides (HDPs) are key components of innate immunity that exert antimicrobial, antibiofilm, and immunomodulatory activities in all higher organisms. Synthetic peptidomimetic analogs were designed to retain the desirable pharmacological properties of HDPs while having improved stability toward enzymatic degradation, providing enhanced potential for therapeutic applications. Lipidated peptide/β-peptoid hybrids [e.g., Pam-(Lys-βNspe) 6 -NH 2 (PM1) and Lau-(Lys-βNspe) 6 -NH 2 (PM2)] are proteolytically stable HDP mimetics displaying anti-inflammatory activity and formyl peptide receptor 2 antagonism in human and mouse immune cells in vitro . Here PM1 and PM2 were investigated for their in vivo anti-inflammatory activity in a phorbol 12-myristate 13-acetate (PMA)-induced acute mouse ear inflammation model. Topical administration of PM1 or PM2 led to attenuated PMA-induced ear edema, reduced local production of the pro-inflammatory chemokines MCP-1 and CXCL-1 as well as the cytokine IL-6. In addition, diminished neutrophil infiltration into PMA-inflamed ear tissue and suppressed local release of reactive oxygen and nitrogen species were observed upon treatment. The obtained results show that these two peptidomimetics exhibit anti-inflammatory effects comparable to that of the non-steroidal anti-inflammatory drug indomethacin, and hence possess a potential for treatment of inflammatory skin conditions.

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Section: Methodsmentioning

confidence: 99%

In vivo Anti-inflammatory Activity of Lipidated Peptidomimetics Pam-(Lys-βNspe)6-NH2 and Lau-(Lys-βNspe)6-NH2 Against PMA-Induced Acute Inflammation

Skovbakke

Masoudi

et al. 2020

Front. Immunol.

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“…Hansen et al modified the synthesis strategy by preparing tetrameric building blocks via solid-phase synthesis, whereas previously, building blocks were used as dimers and prepared in solution phase. [44] The synthesis protocol was based on construction of the tetramer on 2-CTC resin using Fmoc chemistry. This methodology allowed purification-free access to the building blocks and readily purified final oligomers were obtained.…”

Section: Solid-phase Synthesis Of α-Peptide/β-peptoid Hybridsmentioning

confidence: 99%

Solid‐Phase Synthesis of Peptidomimetics with Peptide Backbone Modifications

2021

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Peptidomimetics are a class of compounds with promising pharmacological properties. Peptidomimetics reduce limitations of peptides including low bioavailability, poor stability, and poor cell‐permeability. Peptide backbone modifications are a frequently used manipulation to reach desirable properties of the peptide molecules. The development of accessible synthetic methodologies plays an important role in peptidomimetic progress. Synthesis of peptidomimetics proceeds via solution and solid‐phase synthesis strategies. Solid‐phase organic synthesis serves as a powerful tool for the preparation of peptidomimetic molecules, thus, numerous strategies have been developed over the years. In this review, we discuss solid‐phase synthetic approaches for peptide backbone modifications that were presented in the last two decades.

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“…Some of the particles precipitated in acetonitrile were smaller than the pore size of the glass frit filter funnel (40–90 𝜇m). In addition, unwanted side chain cleavage from the peptoid backbone during the acidic cleavage reaction contributed to the low product yield 33 . Precise control during precipitation and filtration and suppression of the side reactions during the acidic cleavage using milder conditions can result in higher product yields.…”

Section: Figurementioning

confidence: 99%