The design and synthesis of Ala-Glu/iGln mimetics: heterocyclic building blocks for pseudopeptides

Jakopin, Žiga

doi:10.1016/j.tetlet.2014.12.035

Cited by 14 publications

(5 citation statements)

References 23 publications

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“…The incorporation of ester linkages has been shown to result in increased internalization of the compounds. 53 Our preliminary results suggest that diethyl ester derivatives are merely prodrugs since introduction of two 1,2,4-oxadiazole moieties as nonhydrolyzable, bioisosteric replacements of the two diethyl ester moieties 54 resulted in complete loss of NOD2-agonistic activity. 34 Compounds incorporating ester functionalities are most often cleaved with carboxylic ester hydrolases, particularly carboxylesterases.…”

Section: Determination Of Stability Andmentioning

confidence: 99%

Discovery of Nanomolar Desmuramylpeptide Agonists of the Innate Immune Receptor Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Possessing Immunostimulatory Properties

et al. 2018

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Muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, has long been known as the smallest fragment possessing adjuvant activity, on the basis of its agonistic action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). There is a pressing need for novel adjuvants, and NOD2 agonists provide an untapped source of potential candidates. Here, we report the design, synthesis, and characterization of a series of novel acyl tripeptides. A pivotal structural element for molecular recognition by NOD2 has been identified, culminating in the discovery of compound 9, the most potent desmuramylpeptide NOD2 agonist to date. Compound 9 augmented pro-inflammatory cytokine release from human peripheral blood mononuclear cells in synergy with lipopolysaccharide. Furthermore, it was able to induce ovalbumin-specific IgG titers in a mouse model of adjuvancy. These findings provide deeper insights into the structural requirements of desmuramylpeptides for NOD2-activation and highlight the potential use of NOD2 agonists as adjuvants for vaccines.

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Section: Determination Of Stability Andmentioning

confidence: 99%

Discovery of Nanomolar Desmuramylpeptide Agonists of the Innate Immune Receptor Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Possessing Immunostimulatory Properties

et al. 2018

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“…In contrast to mutagenesis, chemical synthesis has provided peptide analogues with no restriction of amino acids [165,169]. The analogues have been produced with unnatural amino acids in both linear and cyclic manner [170].…”

Section: Challenges and Futurementioning

confidence: 99%

Peptide Bacteriocins - Structure Activity Relationships

Etayash¹,

Azmi²,

Dangeti³

et al. 2015

CTMC

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With the growing concerns in the scientific and health communities over increasing levels of antibiotic resistance, antimicrobial peptide bacteriocins have emerged as promising alternatives to conventional small molecule antibiotics. A substantial attention has recently focused on the utilization of bacteriocins in food preservation and health safety. Despite the fact that a large number of bacteriocins have been reported, only a few have been fully characterized and structurally elucidated. Since knowledge of the molecular structure is a key for understanding the mechanism of action and therapeutic effects of peptide, we centered our focus in this review on the structure-activity relationships of bacteriocins with a particular focus in seven bacteriocins, namely, nisin, microcin J25, microcin B17, microcin C, leucocin A, sakacin P, and pediocin PA-1. Significant structural changes responsible for the altered activity of the recent bacteriocin analogues are discussed here.

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“…We have been engaged in the development of NOD ligands, as both agonists and antagonists [21][22][23][24][25][26][27][28], and here we report on a novel series of NOD antagonists. We made use of the existing knowledge of the structure-activity relationships (SARs) of the only NOD2-selective antagonists reported to date, to design and synthesize new compounds based on the benzimidazole scaffold of GSK669.…”

Section: Introductionmentioning

confidence: 99%

Structural features and functional activities of benzimidazoles as NOD2 antagonists

Guzelj

Gobec

Urbančič

et al. 2020

European Journal of Medicinal Chemistry

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The design and synthesis of Ala-Glu/iGln mimetics: heterocyclic building blocks for pseudopeptides

Cited by 14 publications

References 23 publications

Discovery of Nanomolar Desmuramylpeptide Agonists of the Innate Immune Receptor Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Possessing Immunostimulatory Properties

Discovery of Nanomolar Desmuramylpeptide Agonists of the Innate Immune Receptor Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Possessing Immunostimulatory Properties

Peptide Bacteriocins - Structure Activity Relationships

Structural features and functional activities of benzimidazoles as NOD2 antagonists

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