Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00572 (Asn)
 11,732 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity and kinetics of acid-stable protease inhibitor (ASPI) were investigated in the chronic phase of carrageenin-induced inflammation in rats. The ASPI activity was 19.6 +/- 3.1 units/ml in the plasma and 15.4 +/- 2.1 units/ml in the inflammatory exudate. The plasma value was significantly higher than that of the control (11.6 +/- 1.3 units/ml). A kinetics study was performed using purified and radiolabeled rat plasma ASPI, whose NH2-terminal amino acid sequence was Ala-Val-Leu-Pro-Gln-Glu-Asn-Glu-Gly-X-Gly-Ser-Glu-Pro-Leu-Ile-Thr-Gly-Th r-Leu- Lys-Lys-Glu-Asp-Ser-Asn-Gln-Leu-Lys-Tyr-Ser-Glu-Gly-Pro. The half-life of the distributive phase was 4.3 +/- 0.4 min and that of the postdistributive phase (biological half-life) was 42.2 +/- 9.2 min in inflammation. There was no significant difference compared with the values in the control (3.9 +/- 0.4 min and 40.7 +/- 6.5 min, respectively). It appeared that the increase in ASPI in inflammation was not due to prolonged excretion of the inhibitor but to an increased production of it, and ASPI was rapidly distributed to the fluids and tissues.
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PMID:Acid-stable protease inhibitor in chronic phase of carrageenin-induced inflammation in rats. 176 32

We synthesized 10 analogs (1-10) derived from the sequence of [Pmp1,D-Trp2,Arg8]oxytocin, (parent antagonist or PA), (Pmp = beta,beta-pentamethylene-beta-mercaptopropionic acid) which is a potent antagonist (pA2 = 7.77) of the uterotonic effect of oxytocin (OT) in rats, as determined in our uterotonic assay. Eight of the following analogs were designed by replacement of each residue in the PA sequence, other than the residue at position 2, with D-tryptophan: Ac-D-Trp-D-Trp-Ile-Gln-Asn-Val-Pro- Arg-Gly-NH2, (1); [Pmp1,D-Trp(For)2,Arg8] OT, (2); [Pmp1,D-Trp2,D-Trp3,Arg8] OT, (3); [Pmp1,D-Trp2,D-Trp4,Arg8] OT, (4); [Pmp1,D-Trp2,D-Trp5,Arg8] OT, (5); Aaa-D-Trp-Ile-Gln-Asn-D-Trp-Pro-Arg- Gly-NH2, (6); [Pmp1,D-Trp2,D-Trp7,Arg8] OT, (7); [Pmp1,D-Trp2,D-Trp8] OT, (8); [Pmp1,D-Trp2,Arg8,D-Trp9] OT, (9); [Pmp1,D-Trp2,Arg8,D-Trp(For)9] OT, (10). To avoid free mercaptan groups, Val6 was chosen in analog 1 instead of Cys and Aaa1 (Aaa = 1-adamantaneacetic acid) in analog 6 instead of Pmp1. Of the linear analogs, 1 was inactive as an OT antagonist and 6 was a very poor antagonist, with a pA2 = 5.66, but it was more potent than Aaa-D-Trp-Ile-Gln-Asn-Val-Pro-Arg-Gly-NH2, which has a pA2 = 5.33, as we had previously reported. Analog 2, featuring D-Trp(For)2, pA2 = 7.37, was weaker than PA, indicating that the formyl group lowers potency. Analogs 3 and 4 were much weaker than PA, and analog 5 was inactive. Hence, other than at position 2, D-Trp is undesirable in the ring sequence of PA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Some pharmacological properties of cyclic and linear analogs obtained by substituting each residue of an oxytocin antagonist with D-tryptophan. 178 91

An extract of chicken intestine contained neuromedin U-like immunoreactivity (36 pmol/g wet tissue weight). The primary structure of the predominant molecular form (NMU-9), comprising 94% of the total immunoreactivity, was established as: Gly-Tyr-Phe-Phe-Phe-Arg-Pro-Arg- Asn-NH2. This sequence differs from that of pig neuromedin U-8 (NMU-8) by the substitution of Leu3 by Phe and, like the corresponding peptide from the guinea pig, is extended from the NH2-terminus by a Gly residue. A minor component of neuromedin U comprised 25 amino acid residues. An extract of chicken whole brain contained much less NMU-like immunoreactivity (1.5 pmol/g) and the nonpeptide was the only molecular form detected. Synthetic chicken NMU-9 produced a concentration-dependent contraction of smooth muscle from the rat uterus and its effect was unchanged in the presence of tetrodotoxin, atropine and indomethacin. The potency of chicken NMU-9 (EC50 360 +/- 60 nM; mean +/- S.E., n = 6) was approximately 8-fold less than that of pig NMU-8 (EC50 46 +/- 8 nM) but the maximum contraction produced by both agonists was not significantly different.
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PMID:Primary structure and pharmacological activity of a nonapeptide related to neuromedin U isolated from chicken intestine. 178 45

A novel peptide termed locustamyoinhibiting peptide (LOM-MIP) was isolated from brain-corpora cardiaca-corpora allata-suboesophageal ganglion extracts of the locust, Locusta migratoria. The primary structure of this nonapeptide has been determined Ala-Trp-Gln-Asp-Leu-Asn-Ala-Gly-Trp-NH2. LOM-MIP suppresses the spontaneous contractions of the hindgut and oviduct of Locusta migratoria and of the hindgut of Leucophaea maderae. This novel peptide is, however, structurally different from leucomyosuppressin, a hindgut suppressing peptide isolated from Leucophaea maderae heads. LOM-MIP has a Gly-TrpNH2 carboxy-terminal in common with APGWamide, a penis retractor muscle inhibiting peptide isolated from the snail, Lymnea stagnalis. In addition, it shows carboxy-terminal sequence similarities with locust AKH II which ends in AGWamide. No sequence similarities were found with other vertebrate or invertebrate peptides. Synthetic LOM-MIP showed biological as well as chemical characteristics indistinguishable from those of native LOM-MIP.
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PMID:Isolation, identification and synthesis of locustamyoinhibiting peptide (LOM-MIP), a novel biologically active neuropeptide from Locusta migratoria. 179 79

The N-terminal heptadecapeptide of human angiotensinogen (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn-Glu-Ser-Thr-NH2 ), with the C-terminal carboxyl group amidated, was synthesized in order to study the role of Asn-Glu-Ser, a putative carbohydrate binding site, on the hydrolysis by human renin. The synthesis was performed by fragment condensation using the Honzl and Rudinger azide procedure. In our conditions for azide segment condensation, histidine racemization was demonstrated to be negligible for most of the condensation reactions. Human renin liberates angiotensin I from h-angiotensinogen (1-17)-NH2 with a Km value of 3.4 x 10(-5) M, at pH 7.3 and 37 degrees being similar to h-angiotensinogen (1-13), an analog without the carbohydrate binding site. However, the Vmax value of 4.1 x 10(-9) mol/G.U. min is one order of magnitude higher. Porcine pepsin was demonstrated to cleave preferentially Leu10-Val11 bond and, surprisingly, His9-Leu10 as well.
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PMID:Synthesis of human angiotensinogen (1-17) containing one of the putative glycosylation binding sites and its hydrolysis by human renin and porcine pepsin. 179 5

Two protected peptides Boc-Val-Ser(Bzl)-Gln-Asn-Tyr(BrZ)OH and Boc-Val-Ser(Bzl)-Gln-Asn-Tyr(BrZ)-ProOH were synthesized on a resin substituted by 9-(hydroxymethyl)-2-fluoreneacetic acid. After cleavage with piperidine/DMF, desalting, and activation, these peptides were used for the synthesis of 11 analogs of an HIV proteinase nonapeptide substrate Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-NH2 using fragment condensation in solid phase. The fragment condensation was made in an ultrasonic bath. Using only 2 equivalents of the activated peptide in a DMF solution, this reaction was complete in 2 h. All nonapeptides were assayed as substrates for HIV-1 and HIV-2 proteinases.
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PMID:Synthesis of homologous peptides using fragment condensation: analogs of an HIV proteinase substrate. 180 63

To study the structure-activity relationships of neuromedin U-8 (NMU-8) (H-Tyr-Phe-Leu-Phe-Arg-Pro-Arg-Asn-NH2) and to develop a NMU-8 antagonist, twenty-three NMU-8 analogs substituted with Gly or the corresponding D-amino acid(s) at positions 1-8 were synthesized by solid-phase techniques. On isolated chicken crop preparations, the contractile activity of the synthetic NMU-8 analogs was compared with that of NMU-8 and their antagonistic activity was assayed against NMU-8. The replacement of Phe2, Phe4, Arg5, Pro6, Arg7 or Asn8 with Gly brought about a drastic decrease of the agonistic activities. Substitution of the corresponding D-amino acid residue for Phe2, Phe4, Arg5, Pro6 or Asn8 caused a marked decrease of the agonistic activities, while the replacement of Tyr1 with D-form enhanced the activity. It was further revealed that [D-Pro6]-NMU-8 and [D-Leu3, D-Pro6]-NMU-8 exerted a non-competitive antagonistic activity against NMU-8 with x values of 5.22 +/- 0.12 and 5.34 +/- 0.09, respectively. [D-Phe2, D-Pro6]-NMU-8, [D-Arg5, D-Pro6]-NMU-8 and [D-Pro6, D-Asn8]-NMU-8 showed a very weak antagonism. The results indicated that 1) the side chain of each amino acid at positions 2, 4, 5, 6, 7 and 8 of NMU-8 is of relative importance for the expression of the contractile activity, and 2) [D-Pro6]-NMU-8 and its four analogs acted as an antagonist against NMU-8.
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PMID:Agonistic and antagonistic activities of neuromedin U-8 analogs substituted with glycine or D-amino acid on contractile activity of chicken crop smooth muscle preparations. 180 45

Pancreatic polypeptide (PP) has been purified from extracts of the pancreas of four species of odd-toed ungulates (Perissodactyla): Przewalski's horse, mountain zebra, white rhinoceros, and mountain tapir. The amino acid sequence of Przewalski's horse pancreatic polypeptide was established as Ala-Pro-Met-Glu-Pro-Val-Tyr-Pro-Gly-Asp10-Asn- Ala-Thr-Pro-Glu-Gln-Met-Ala-Gln-Tyr20-Ala-Ala-Glu-Leu-Arg-Arg-Tyr- Ile-Asn-Met30 - Leu-Thr-Arg-Pro-Arg-Tyr.NH2. Zebra PP was identical to Przewalski's horse PP, rhinoceros PP contained three substitutions relative to the horse (Ser for Ala1, Leu for Met3, and Glu for Gln16), and tapir PP contained one substitution relative to the horse (Leu for Met3). On the basis of morphological characteristics and the fossil record, the rhinocerotids are classified with the tapirids in the suborder Ceratomorpha, whereas the horse and zebra belong to a separate suborder, Hippomorpha. On the basis of structural similarity of the PP molecules, however, it would appear that the tapir is more closely related to the horse than to the rhinoceros. These observations provide a further example of the need for extreme caution when inferring taxonomic or phylogenetic relationships between species from the structures of homologous peptides.
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PMID:Primary structure of pancreatic polypeptide from four species of Perissodactyla (Przewalski's horse, zebra, rhino, tapir). 180 25

A 41 amino acid peptide, probably identical in structure to human corticotropin releasing factor, was isolated from 70 equine hypothalami by methanol extraction, immunoaffinity chromatography and single step of reverse phase HPLC. The amino acid sequence was determined by gas phase sequence analysis. Probable carboxyl terminal amidation was demonstrated by similar retention times for equine and human corticotropin releasing factor on reverse phase HPLC at pH 8. The likely structure of equine corticotropin releasing factor is: Ser-Glu-Glu-Pro-Pro- Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg- Ala-Glu - Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-Glu-Ile-Ile-NH2. The purified peptide is equipotent with human corticotropin releasing factor in an in vitro bioassay and in a human plasma binding protein assay.
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PMID:Structure of equine corticotropin releasing factor. 181 30

The deamidation reaction of Asn side chain was studied in the presence of the chemicals usually used at high concentration in the purification and crystallization of peptides and proteins. All the experiments were performed on the model peptide Boc-L-Asn-Gly-Gly-NH2. The pathway of the reaction is not affected by the medium used; in all cases it proceeds through a succinimide intermediate giving a mixture of isoaspartyl and aspartyl peptide. However, the rate of the reaction significantly depends on the solvent: the addition of organic solvents to an aqueous solution of the peptide has the general effect of decreasing the reaction rate, which, on the other hand, is strongly enhanced by a high concentration of organic and inorganic buffers. Only a minor influence is exerted by aprotic salts and polyethylene glycol.
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PMID:Deamidation via cyclic imide of asparaginyl peptides: dependence on salts, buffers and organic solvents. 182 3


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