Therapeutic potential of natural product signal transduction agents

Koehn, Frank E.

doi:10.1016/j.copbio.2006.09.006

Cited by 14 publications

(9 citation statements)

References 51 publications

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“…In particular, the upregulation of peptidyl prolyl cis‐trans isomerase A, is noted here. Immunophilins bind natural product signal transduction modulators or immunophilin ligands (Bell, Monaghan & Page ; Koehn ). The role of this protein is not characterized in Atlantic salmon, given its marked upregulation in fish fed functional feeds; a further investigation of the function of this protein and its role in mediating a possible immunostimulatory role of functional feed ingredients in fish seems to be warranted.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of epidermal mucus from sea lice–infected Atlantic salmon, Salmo salar L.

Provan

Jensen

Uleberg

et al. 2013

Journal of Fish Diseases

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Health diets that contain immunostimulants and other functional ingredients can strengthen the immune response in Atlantic salmon, Salmo salar, and thereby reduce sea lice, Lepeophtheirus salmonis, infection levels. Such diets can be used to supplement other treatments and will potentially reduce the need for delousing and medication. A sea lice infection trial was conducted on fish with an average weight of 215 g. One control diet and four experimental diets containing functional ingredients were produced. The diets were fed to salmon for 4 weeks before infection with sea lice copepodids. When lice had developed to chalimus III/IV, 88 fish per diet were examined for lice loads. Mucus samples from fish fed the different diets were taken before and after lice infection. Mass spectrometry-based proteomics was used to characterize the protein composition in the epidermal mucus of Atlantic salmon and to identify quantitative alterations in protein expression. Multivariate analysis of the generated data sets was performed to identify protein biomarkers. Putative biomarkers associated with functional feed intake and with sea lice infection have been identified and can form the basis for strategic validation experiments with selected functional feeds.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of epidermal mucus from sea lice–infected Atlantic salmon, Salmo salar L.

Provan

Jensen

Uleberg

et al. 2013

Journal of Fish Diseases

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“…These natural products have been key probes for understanding PPIase function and were even used to identify members of the PPIase family . Previous reviews have summarized the structure and function of PPIases, , their roles in disease, − and the history of natural products as inhibitors. − Here, we only briefly discuss these topics before focusing on understanding how natural products have informed recent developments in the search for selective, potent PPIase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Peptidyl-Proline Isomerases (PPIases): Targets for Natural Products and Natural Product-Inspired Compounds

2016

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Peptidyl-proline isomerases (PPIases) are a chaperone superfamily comprising the FK506-binding proteins (FKBPs), cyclophilins, and parvulins. PPIases catalyze the cis/trans isomerization of proline, acting as a regulatory switch during folding, activation, and/or degradation of many proteins. These “clients” include proteins with key roles in cancer, neurodegeneration, and psychiatric disorders, suggesting that PPIase inhibitors could be important therapeutics. However, the active site of PPIases is shallow, solvent-exposed, and well conserved between family members, making selective inhibitor design challenging. Despite these hurdles, macrocyclic natural products, including FK506, rapamycin, and cyclosporin, bind PPIases with nanomolar or better affinity. De novo attempts to derive new classes of inhibitors have been somewhat less successful, often showcasing the “undruggable” features of PPIases. Interestingly, the most potent of these next-generation molecules tend to integrate features of the natural products, including macrocyclization or proline mimicry strategies. Here, we review recent developments and ongoing challenges in the inhibition of PPIases, with a focus on how natural products might inform the creation of potent and selective inhibitors.

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“…In all cases, modifications were made in the one area, the C-43 alcoholic hydroxyl group that avoids both the FKBP-12 and the target of rapamycin (TOR) binding sites, since modifications in other areas would negate the basic biological activity of this molecule . For a further discussion on modification of molecules from a similar biosynthetic source (polyketide immunophilin ligands) one should consult the recent review by Koehn …”

Section: Discussion Of Specific Topicsmentioning

confidence: 99%

Natural Products as Leads to Potential Drugs: An Old Process or the New Hope for Drug Discovery?

2008

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Therapeutic potential of natural product signal transduction agents

Cited by 14 publications

References 51 publications

Proteomic analysis of epidermal mucus from sea lice–infected Atlantic salmon, Salmo salar L.

Proteomic analysis of epidermal mucus from sea lice–infected Atlantic salmon, Salmo salar L.

Peptidyl-Proline Isomerases (PPIases): Targets for Natural Products and Natural Product-Inspired Compounds

Natural Products as Leads to Potential Drugs: An Old Process or the New Hope for Drug Discovery?

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