Small lipidated anti-obesity compounds derived from neuromedin U

Micewicz, Ewa D.; Bahattab, Omar; Willars, Gary B.; Waring, Alan J.; Navab, Mohamad; Whitelegge, Julian P.; McBride, William H.; Ruchala, Piotr

doi:10.1016/j.ejmech.2015.07.020

Cited by 17 publications

(17 citation statements)

References 104 publications

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“…Next, the peptide was cleaved further at the same position Previously, the stability of some NMU-based molecules was already reported in literature. Lipidation of NMU-8 markedly increased its half-life in mouse plasma as compared to hNMU [21]. Moreover, when the effect on proteolytic stability was studied of molecules without high molecular carriers, improved resistance towards degradation was observed as well.…”

Section: In Vitro Plasma Stabilitymentioning

confidence: 94%

“…Additionally, other novel analogs based on the truncated form of NMU, such as small lipidated NMUanalogs [21] and PEGylated NMU-8 [22], were already described to have potent anorectic and antiobesity effects. Several molecules based on the long version of NMU were synthesized as well, including a NMU-25 conjugate with human serum albumin [23], a PEGylated NMU-25 derivative [24] and lipidated NMU-25 analogs [25].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Development of potent and proteolytically stable human neuromedin U receptor agonists

Prins

Martin

Wanseele

et al. 2018

European Journal of Medicinal Chemistry

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Neuromedin U (NMU) is a highly conserved endogenous peptide that is involved in a wide range of physiological processes such as regulation of feeding behavior, the stress response and nociception. The major limitation to use NMU as a therapeutic is its short half-life. Here, we describe the development of a set of novel NMU-analogs based on NMU-8, by introducing unnatural amino acids into the native sequence. This approach shows that it is possible to generate molecules with increased potency and improved plasma stability without major changes of the peptidic nature or the introduction of large conjugates. When compared to the native NMU-8 peptide, compounds 16, 18 and 20 have potent agonist activity and affinity for both NMU receptors. Selectivity towards NMUR1 was observed when the Phe residue in position 4 was modified, whereas higher potencies at NMUR2 were found when substitutions of the Pro residue in position 6 were executed. To study the effect of the modifications on the proteolytic stability of the molecules, an in vitro stability assay in human plasma at 37 °C was performed. All analyzed analogs possessed an increased resistance against enzymatic degradation in human plasma resulting in half-lifes from 4 min for NMU-8, up to more than 23 h for compound 42.

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Section: In Vitro Plasma Stabilitymentioning

confidence: 94%

Section: Accepted Manuscriptmentioning

confidence: 99%

Development of potent and proteolytically stable human neuromedin U receptor agonists

Prins

Martin

Wanseele

et al. 2018

European Journal of Medicinal Chemistry

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“…Obesity has turned into one of the most serious health problems in the current century and it is believed to elevate the probability of heart disease, type-2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis, among others (Micewicz et al, 2015). There has thus been a great deal of interest in anti-obesity drugs with satiating and appetite suppressant effects; however, the use of these drugs is limited due to their adverse effects such as depression and cardiovascular risks (Ziauddeen and Fletcher, 2013).…”

Section: Anti-obesitymentioning

confidence: 99%

“…More recently, (Micewicz et al, 2015) revealed that NM4-C 16 , a truncated/lipid-conjugated neuromedin U (NmU) analog, has strong appetite suppressing effects in a diet-induced obese (DIO) mouse model; it is noteworthy that Neuromedin U (NmU) is an endogenous peptide with various physiological effects.…”

Section: Anti-obesitymentioning

confidence: 99%

Peptides: Production, bioactivity, functionality, and applications

Hajfathalian

Ghelichi

Moreno

et al. 2017

Critical Reviews in Food Science and Nutrition

138

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Production of peptides with various effects from proteins of different sources continues to receive academic attention. Researchers of different disciplines are putting increasing efforts to produce bioactive and functional peptides from different sources such as plants, animals, and food industry by-products. The aim of this review is to introduce production methods of hydrolysates and peptides and provide a comprehensive overview of their bioactivity in terms of their effects on immune, cardiovascular, nervous, and gastrointestinal systems. Moreover, functional and antioxidant properties of hydrolysates and isolated peptides are reviewed. Finally, industrial and commercial applications of bioactive peptides including their use in nutrition and production of pharmaceuticals and nutraceuticals are discussed.

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“…During digestion, BP must cross the gastrointestinal barrier and survive enzyme degradation in order to have a positive health effect [ 47 ]. Depending on the sequence of the amino acid sequence, BP render many functional, physiological, and therapeutic properties, including antihypertensive [ 48 ], antioxidant [ 48 , 49 ], anti-obesity [ 50 ], antifungal, antiviral, immunomodulatory [ 51 ], antimicrobial [ 51 , 52 ], anticoagulant [ 53 ], anti-inflammatory [ 54 ], antidiabetic, iron- and calcium-binding activities [ 55 ], antiproliferative [ 56 ] and chelating effects [ 57 ]. They also account for the taste of food and the inhibition of enzymes involved in developing diseases.…”

Section: Antioxidative Peptidesmentioning

confidence: 99%

Exploring Molecular Insights of Cereal Peptidic Antioxidants in Metabolic Syndrome Prevention

et al. 2021

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The prevalence of metabolic syndrome (MetS) is presently an alarming public health problem globally. Oxidative stress has been postulated to be strongly correlated with MetS, such as type 2 diabetes, obesity, hypertension, cardiovascular diseases, and certain cancers. Cereals are important staple foods which account for a huge proportion of the human diet. However, owing to recent growing demand and the search for natural antioxidants for the prevention and management of MetS, cereal peptides have gained increasing attention for developing functional ingredients or foods with substantial antioxidant properties. This review explores the current production techniques for cereal peptidic antioxidants and their potential mechanism of action in the prevention and management of MetS.

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Small lipidated anti-obesity compounds derived from neuromedin U

Cited by 17 publications

References 104 publications

Development of potent and proteolytically stable human neuromedin U receptor agonists

Development of potent and proteolytically stable human neuromedin U receptor agonists

Peptides: Production, bioactivity, functionality, and applications

Exploring Molecular Insights of Cereal Peptidic Antioxidants in Metabolic Syndrome Prevention

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