Structure-Activity Relationships of Neuromedin U.I. Contractile Activity of Dog Neuromedin U-Related Peptides on Isolated Chicken Crop Smooth Muscle.

Sakura, Naoki; Kurosawa, Katsuro; Hashimoto, Tadashi

doi:10.1248/cpb.43.1148

Cited by 15 publications

(17 citation statements)

References 2 publications

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“…The same result was obtained for rat neuromedin U-23, 5,14,15) dog neuromedin U-8 bearing pGlu at the N-terminal, 6,16) and [Gly 1 ]-neuromedin U-8, 17) (data not shown). The displacement curves of synthetic N-terminally deleted analogs 5) such as H-Phe-LeuPhe-Arg-Pro-Arg-Asn-NH 2 , H-Leu-Phe-Arg-Pro-Arg-Asn-NH 2 , and H-Phe-Arg-Pro-Arg-Asn-NH 2 showed reduced but considerable cross-reactivity.…”

supporting

confidence: 79%

“…The displacement curves of synthetic N-terminally deleted analogs 5) such as H-Phe-LeuPhe-Arg-Pro-Arg-Asn-NH 2 , H-Leu-Phe-Arg-Pro-Arg-Asn-NH 2 , and H-Phe-Arg-Pro-Arg-Asn-NH 2 showed reduced but considerable cross-reactivity. The C-terminally deleted analogs H-Tyr-Phe-Leu-Phe-Arg-Pro-Arg-OH 6) and [Gly 8 ]-neuromedin U-8 17) showed no activity in displacing the tracer. In this neuromedin U RIA system, the deamidation products 2, 3, and 4 had no cross-reactivity.…”

mentioning

confidence: 98%

“…Biological Activity of Neuromedin U-8 Analogs The biological activity of synthetic peptides was evaluated by a contraction assay on a chicken crop smooth muscle preparation as described in a previous paper. 6) Briefly, a strip of smooth muscle from the chicken crop was mounted longitudinally at a resting tension of 0.5 g in an organ bath (10 ml) containing Tyrode's solution at 30°C. The tissue preparation was equilibrated for 60 min, and was then challenged twice with carbachol (2ϫ10 Ϫ6 M), and once with X-Asn-NH 2 (1) added cumulatively up to 3ϫ10 Ϫ6 M. After re-equilibration for 30-40 min, increasing concentrations of 1 were added up to 3ϫ10…”

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confidence: 99%

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Structure-Activity Relationships of Neuromedin U. V. Study on the Stability of Porcine Neuromedin U-8 at the C-Terminal Asparagine Amide under Mild Alkaline and Acidic Conditions

Kawai

Shibata

Kurosawa

et al. 2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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confidence: 79%

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confidence: 98%

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confidence: 99%

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Structure-Activity Relationships of Neuromedin U. V. Study on the Stability of Porcine Neuromedin U-8 at the C-Terminal Asparagine Amide under Mild Alkaline and Acidic Conditions

Kawai

Shibata

Kurosawa

et al. 2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Presumably, changes in the N-terminal region alter the 3-dimensional structure of the peptide and favor a conformation with enhanced activity. Conversely, modification of the N terminus may result in increased resistance to degradation by peptidases, thereby increasing the peptide half-life (11,12 ). Lastly, posttranslational amidation of the C-terminal amino acid is also essential for NmU activity, because deamidated forms are unable to induce smooth muscle contraction or intracellular Ca 2ϩ influx (9,13,14 ).…”

Section: Structurementioning

confidence: 99%

Neuromedin U: A Multifunctional Neuropeptide with Pleiotropic Roles

2015

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BACKGROUND Neuromedin U (NmU) belongs to the neuromedin family, comprising a series of neuropeptides involved in the gut–brain axis and including neuromedins B and C (bombesin-like), K (neurokinin B), L (neurokinin A or neurotensin), N, S, and U. CONTENT Although initially isolated from porcine spinal cord on the basis of their ability to induce uterine smooth muscle contraction, these peptides have now been found to be expressed in several different tissues and have been ascribed numerous functions, from appetite regulation and energy balance control to muscle contraction and tumor progression. NmU has been detected in several species to date, particularly in mammals (pig, rat, rabbit, dog, guinea pig, human), but also in amphibian, avian, and fish species. The NmU sequence is highly conserved across different species, indicating that this peptide is ancient and plays an important biological role. Here, we summarize the main structural and functional characteristics of NmU and describe its many roles, highlighting the jack-of-all-trades nature of this neuropeptide. SUMMARY NmU involvement in key processes has outlined the possibility that this neuropeptide could be a novel target for the treatment of obesity and cancer, among other disorders. Although the potential for NmU as a therapeutic target is obvious, the multiple functions of this molecule should be taken into account when designing an approach to targeting NmU and/or its receptors.

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“…12) as the main product, and [Glu 1 ]-NMU-8 (2b), 11) d-NMU-8-OH (2c), 13) [Asp 8 ]-d-NMU-8-OH (2d), 13) and d-NMU-8 (2-8)-OH (2e) as minor products (Fig. 5B).…”

Section: Resultsmentioning

confidence: 99%

Hydrolytic Cleavage of Pyroglutamyl-peptide Bond. V. Selective Removal of Pyroglutamic Acid from Biologically Active Pyroglutamylpeptides in High Concentrations of Aqueous Methanesulfonic Acid

Kobayashi

Ohki

Okimura

et al. 2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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Biologically active peptides bearing pyroglutamic acid residue (pGlu) at the N-terminal are widely known. The removal of pGlu residue from a pGlu-X-peptide (X, amino acid residue at position 2) is required for the primary structure determination by Edman degradation. Our previous studies indicated that pGlu-X peptide bond is highly sensitive to mild acidic conditions, generating not only the ring opened product (H-Glu-X-peptide) at the pyrrolidone moiety of pGlu, but also the cleavage product (H-X-peptide) at pGlu-X linkage.1,2) High selectivity to remove pGlu-OH from synthetic model pGlu-X-peptides was attained in concentrated hydrochloric acid 3) and in 70% aqueous methanesulfonic acid (MSA). 4,5) The aim of this study was to compare the selectivity of the cleavage reaction at pGlu-X bond in aqueous MSA with various internal peptide bonds in five biologically active pGlu-X-peptides, containing well-known acid sensitive amide bonds. The sequence of these peptides, namely, gonadotropin-releasing hormone (Gn-RH; 1), 6) dog neuromedin U-8 (d-NMU-8; 2), 7) physalaemin (PH; 3), 8) a bradykinin potentiating peptide (BPP-5a; 4), 9) and neurotensin (NT; 5), 10) are shown in Fig. 1. ExperimentalGeneral and Apparatus HPLC analysis was performed on a module consisted of a 7125 injector (Rheodyne Inc., U.S.A.), a 616 pump, a 600 s controller, a 486 tunable absorbance detector, a 717 plus autosampler, and an SDM solvent degas module (all from Waters Corp., Milford, MA, U.S.A.).Amino acid analysis was conducted on a 7300 Model amino acid analyzer system (Beckman Instruments Ltd., Fullerton, CA, U.S.A.). The hydrolysis of a synthetic peptide was performed by 6 M HCl vapor at 130°C for 3 h. Fast-atom bombardment mass spectra (FAB-MS) were obtained on a JMS-DX300 mass spectrometer (JEOL Ltd., Tokyo, Japan). Optical rotations of the peptides were measured with a DIP-370 digital polarimeter (Nippon Bunko Co., Ltd., Tokyo, Japan). HP-TLC analysis was carried out on precoated silica gel plates (Kieselgel 60; Merck, Darmstadt, Germany).Peptides Syntheses of Gn-RH (1), PH (3), BPP-5a (4) and NT (5) (Fig. 1) and various fragment peptides related to these biologically active peptides (Figs. 2,5,6,8,9) were carried out according to a method previously reported for d-NMU-8 (2).11) Protected peptide resins were constructed by Boc strategy either on a benzhydrylamine resin or a chloromethylated polystyrene resin (Peptide Institute Inc., Osaka, Japan) using a peptide synthesizer (ABI 433A; Applied Biosystems, Foster City, CA, U.S.A.). Side chain protected Boc-amino acid derivatives (Watanabe Chemical Industries Ltd., Hiroshima, Japan) were Tyr(BrZ), Arg(Tos), Asp(OcHex), Lys(Cl-Z), Ser(Bzl), His(Bom) and Glu(OBzl). The protected peptide resins were treated with anhydrous liquid hydrogen fluoride (HF) containing 10% anisole under ice cooling for 45 min in a Teflon HF apparatus (Peptide Institute Inc., Osaka, Japan). After evaporation of HF in vacuo, the residual peptides were purified by HPLC, using a column of YMC-pack ODS-AM S-5 120 Å (20...

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Structure-Activity Relationships of Neuromedin U.I. Contractile Activity of Dog Neuromedin U-Related Peptides on Isolated Chicken Crop Smooth Muscle.

Cited by 15 publications

References 2 publications

Structure-Activity Relationships of Neuromedin U. V. Study on the Stability of Porcine Neuromedin U-8 at the C-Terminal Asparagine Amide under Mild Alkaline and Acidic Conditions

Structure-Activity Relationships of Neuromedin U. V. Study on the Stability of Porcine Neuromedin U-8 at the C-Terminal Asparagine Amide under Mild Alkaline and Acidic Conditions

Neuromedin U: A Multifunctional Neuropeptide with Pleiotropic Roles

Hydrolytic Cleavage of Pyroglutamyl-peptide Bond. V. Selective Removal of Pyroglutamic Acid from Biologically Active Pyroglutamylpeptides in High Concentrations of Aqueous Methanesulfonic Acid

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