| 3667077 |
Cyclic peptides. XXVI. Synthesis of AM-toxin II analogs by cyclization through ester bond formation |
None |
Int J Pept Protein Res |
Cyclic peptides. XXVI. Synthesis of AM-toxin II analogs by cyclization through ester bond formation
Abstract
- In order to explore the route for the preparation of cyclodepsipeptide by cyclization through an ester bond formation, two analogs of AM-toxin II, cyclotetradepsipeptide, were synthesized. As a preliminary experiment, synthesis of L-Phe3, L-Ser(Bzl)4-AM-toxin II, containing L-Phe and L-Ser(Bzl) in place of L-App (2-amino-5-phenyl-pentanoic acid) and delta Ala (alpha, beta-dehydroalanine), respectively, was attempted. Cyclization of H-L-Hmb-L-Phe-L-Ser(Bzl)-L-Ala-OH in CH2Cl2 at 10 mM concentration using water-soluble carbodiimide (EDC) and 4-dimethylaminopyridine (DMAP) successfully gave a cyclic monomer in 16% yield. Cyclization of H-L-Hmb-L-App-L-Ser(Bzl)-L-Ala-OH under the same conditions also afforded a cyclic monomer, L-Ser(Bzl)4AM-toxin II, in 19% yield. Analytical parameters of these cyclic monomers obtained were identical to those of the authentic samples obtained by cyclization through a peptide bond formation.
|
| 3680248 |
Characterization of the promoter region of the human insulin receptor gene. Evidence for promoter activity. |
10.1016/s0021-9258(18)47714-9 |
J. Biol. Chem. |
Characterization of the promoter region of the human insulin receptor gene. Evidence for promoter activity.
Abstract
- Recombinant clones containing the promoter region of the human insulin receptor gene were isolated from genomic libraries derived from nondiabetic persons. A 1.5-kilobase pair fragment of the 5'-flanking region was sequenced. One transcriptional start site, located at 203 bases upstream from the start of translation was identified by nuclease S1 mapping and the primer extension experiment using the human insulin receptor mRNA. The bacterial chloramphenicol acetyltransferase assay revealed that a 573-base pair fragment immediately preceding the ATG has promoter activity and that the transcript initiates from the normal start site of the insulin receptor gene in the COS cells. The promoter region contains neither a "TATA box" nor a "CAAT box," has an extremely high G + C content, and contains seven central components of potential Sp 1 binding sites (GGGCGG or CCGCCC). These features are common to those found in the regulatory regions of a class of constitutively expressed "housekeeping" genes. A comparison between the promoter sequence of the human insulin receptor and those of other "housekeeping" genes revealed the presence of homologous sequences among these genes, in addition to the potential Sp 1 binding sites.
|
| 3697361 |
Synthetic amatoxin analogue. A two-dimensional proton NMR study of S-deoxy-(Ile3)-(D-Ala7)-amaninamide |
10.1016/0167-4838(86)90253-0. |
Biochim Biophys Acta |
Synthetic amatoxin analogue. A two-dimensional proton NMR study of S-deoxy-(Ile3)-(D-Ala7)-amaninamide
Abstract
- The effect of substitution of L and D amino acids in amatoxin analogues is discussed in this paper. The structure of the analog where D-alanine substitutes for glycine in position 7 has been worked out in solution by two-dimensional NMR methods using a 500 MHz instrument. The combined use of COSY and NOESY two-dimensional spectra allows a clear assignment of the resonances. The use of the coupling constants permits the calculation of the phi angles of the backbone. The NOE effects reveal the through-space contacts between protons of different peptide units, thus determining the rigidity of the amatoxin structure. On these grounds it has been possible to elucidate the conformation of the amatoxin analogue that resembles very closely that of beta-amanitin, thus explaining the high inhibitory activity toward RNA polymerase B.
|
| 3699982 |
Calcium binding cyclic hexapeptide. Crystal structure of cyclo-(L-prolyl-glycyl)3 calcium complex |
None |
Int J Pept Protein Res |
Calcium binding cyclic hexapeptide. Crystal structure of cyclo-(L-prolyl-glycyl)3 calcium complex
Abstract
- The synthetic cyclic hexapeptide (L-prolyl-glycyl)3 forms a 2:1 complex with Ca2+ ion. The cation is sandwiched between the two peptide molecules. The glycyl carbonyls from each of the peptides are octahedrally coordinated to the cation with an average calcium oxygen coordination distance of 2.26A. Both the molecules coordinating to the calcium ion have three fold symmetry, but show significant conformational differences. In one of the peptides of the sandwich, the alternate carbonyls point to the opposite sides of the peptide ring while in the other, all the six carbonyls point to the same side of the ring. Three NH ... O hydrogen bonds between the peptides add to the stability of the sandwich.
|
| 3718926 |
Alloviroidin, the naturally occurring toxic isomer of the cyclopeptide viroidin |
10.1021/bi00358a019. |
Biochemistry |
Alloviroidin, the naturally occurring toxic isomer of the cyclopeptide viroidin
Abstract
- A novel toxic cyclopeptide from Amanita suballiacea (Murr.) mushrooms that possesses structural features similar to viroidin is described. This peptide, alloviroidin, is identical with viroidin in mass, affinity for actin, and all amino acids except for one. The single discernible difference between the two peptides exists in the configuration at carbon 4 of the 4,5-dihydroxyleucine residues, as shown by a combination of chemical modification and magnetic resonance experiments. The configuration of this residue in viroidin is similar to that of phalloidin and is 2S,4R, while that in alloviroidin is established to be 2S,4S. This peptide is thus unique in its hydroxylation pattern among both the virotoxins and phallotoxins and may be an intermediate for more highly hydroxylated virotoxins, such as viroisin.
|
| 3748373 |
Psychotropic properties of oxytocin |
10.1007/BF01186517. |
Neurosci Behav Physiol |
Psychotropic properties of oxytocin
Abstract
|
| 3753928 |
Hypnogenic activity of the cyclic structural analog of the delta-sleep-inducing peptide |
None |
Dokl Akad Nauk SSSR |
Hypnogenic activity of the cyclic structural analog of the delta-sleep-inducing peptide
Abstract
|
| 3759343 |
Water structure in Phe4 Val6 antamanide X 12H2O crystallized from dioxane |
10.1111/j.1399-3011.1986.tb03224.x. |
Int J Pept Protein Res |
Water structure in Phe4 Val6 antamanide X 12H2O crystallized from dioxane
Abstract
- Crystals of Phe4 Val6 antamanide (cyclic ValProProPhePhe2) grown from dioxane/H2O, with space group P21212 and cell parameters a = 15.099(4), b = 22.008(5) and c = 11.024(3) A, are almost identical to crystals grown from H2O/acetone, the structure of which was determined a number of years ago. Per peptide molecule there are the equivalent of 12 water molecules occupying 16 sites in both crystals; however, in the new investigation a number of water molecules present at one-half occupancy have been found in different positions than in the earlier analysis. The interpretation of the hydrogen bonding between peptide/water and between water/water is much more satisfactory. Pentagonal water assemblies are present in the solvent channel. There is a distinct indication of the occurrence of a bifurcated bond between two water molecules, as well as the presence of three-center hydrogen bonds joining three water molecules. This may be the first experimental example of a bifurcated bond between two water molecules.
|
| 3759958 |
Prothrombin fragment 1 X 2 X 3, a major product of prothrombin activation in human plasma. |
10.1016/s0021-9258(18)69292-0 |
J. Biol. Chem. |
Prothrombin fragment 1 X 2 X 3, a major product of prothrombin activation in human plasma.
Abstract
- The conversion of the blood coagulation zymogen prothrombin to thrombin is associated with the production of several cleavage intermediates and products. In contrast to earlier studies of prothrombin cleavage in chemically defined systems, the current investigation examines the fragmentation of human prothrombin in normal plasma. Radiolabeled prothrombin was added to platelet-poor relipidated normal human plasma, and clotting was initiated with the addition of Ca(II) and kaolin. Analysis of the radiolabeled prothrombin cleavage products by polyacrylamide gel electrophoresis in the presence of dodecyl sulfate and beta-mercaptoethanol identified a heretofore unobserved product of prothrombin activation with an apparent molecular weight of 45,000. This product was identified as fragment 1 X 2 X 3, the NH2-terminal 286 amino acids of prothrombin. The product was isolated from a prothrombin digest by immunoaffinity chromatography using anti-prothrombin:Ca(II) antibodies and by preparative gel electrophoresis. Its amino-terminal sequence is identical to that of prothrombin. Digestion of this product with either Factor Xa or thrombin yields, at a minimum, fragment 1 X 2 and fragment 1. Amino-terminal sequence analysis of the products obtained by digestion with Factor Xa of the unknown activation product indicated 3 amino acid residues at each cycle consistent with the presence of fragment 1, fragment 2, and fragment 3. To unambiguously identify the COOH-terminal amino acid sequence of the product, its factor Xa digestion products were separated by reverse-phase high performance liquid chromatography. Edman degradation of one peptide revealed the complete sequence of fragment 3. On this basis, we identify the Mr 45,000 polypeptide as fragment 1 X 2 X 3 and indicate that it is a prominent product of prothrombin conversion to thrombin when activation occurs in plasma.
|
| 3760747 |
3H9-desglycinamide,8-arginine vasopressin: metabolism and in-vivo fate |
10.1677/joe.0.1100557. |
J Endocrinol |
3H9-desglycinamide,8-arginine vasopressin: metabolism and in-vivo fate
Abstract
- Half-lives based on the disappearance of 3H9-desglycinamide,8-arginine vasopressin (3HDGAVP) following in-vitro incubation in plasma were 1.7 h (dog), 5.8 h (rat) and greater than 12 h (man). For all three species, and particularly dogs, biotransformation of the peptide in plasma occurred predominantly through carboxypeptidase activities, leading to the accumulation of AVP-(1-7). Disappearance of 3HDGAVP from rat blood after a single i.v. injection followed a biphasic decay with half-lives of 2.2 +/- 0.8 (S.D.) min (distribution phase) and 14.4 +/- 1.2 min (elimination phase). The central and peripheral volumes of distribution were high and of the same order of magnitude, being 0.21 and 0.25 litres/kg respectively. Blood clearance values ranged from 36 to 45 ml/min per kg. In addition to 3HAVP-(1-7), 3Htyrosine was also found to be a major radioactive metabolite in blood. Compared with i.v. dosing, the s.c. route of administration for 3HDGAVP resulted in longer-lasting peptide levels in blood which persisted for up to 4-5 h after injection. Maximal concentrations were reached at 7.5 min, whereafter they declined bi-exponentially with terminal half-lives of 31.1 +/- 8.7 min. The mean bioavailability for DGAVP was almost 100%, demonstrating virtually complete absorption from the s.c. injection site.
|
| 3769923 |
Epidermin: sequencing of a heterodetic tetracyclic 21-peptide amide antibiotic |
10.1111/j.1432-1033.1986.tb09933.x. |
Eur J Biochem |
Epidermin: sequencing of a heterodetic tetracyclic 21-peptide amide antibiotic
Abstract
- Epidermin is a large peptide antibiotic, which is synthesized in the ribosome via a precursor protein, followed by enzymatic modifications. It was isolated from the culture filtrate of Staphylococcus epidermidis Tü 3298 by adsorption on Amberlite XAD-8. The basic heneicosapeptide amide was chromatographed on Sephadex LH-20 and purified to homogeneity via multiplicative counter-current distributions in one acidic and one neutral system. Tryptic digestion gave the soluble N-terminal fragment epidermin-(1-13)-peptide (P1) and the insoluble C-terminal fragment 2-oxobutyryl-epidermin-(15-21)-peptide amide (P2), each possessing two sulfide ring systems. The heterodetic rings consisted of meso-lanthionine and (2S,3S, 6R)-3-methyllanthionine (P1), meso-lanthionine and C-terminally the new amino acid S-(2-aminovinyl)-D-cysteine (P2). The complex sequence was elucidated via a combination of desulfurization with Raney nickel, enzymatic and acidolytic degradations, gas-phase sequencing, fast-atom bombardment and field-desorption mass spectrometry and NMR spectroscopy.
|
| 3771100 |
Desaminopenicillamine tocinoic acid derivatives--inhibitors of oxytocin |
10.1111/j.1399-3011.1986.tb03242.x. |
Int J Pept Protein Res |
Desaminopenicillamine tocinoic acid derivatives--inhibitors of oxytocin
Abstract
- Tocinoic acid analogs with penicillamine in place of one or both of the cysteine residues have been studied and 1-beta-mercaptopropionic acid, 6-penicillamine tocinoic acid (dPen6TA) and 1-beta,beta-dimethyl-beta-mercaptopropionic acid, 6-penicillamine tocinoic acid (dPen1Pen6TA) have been synthesized in solution. Biological activities of these 2 compounds and those of the previously synthesized 1-beta,beta-dimethyl-beta-mercaptopropionic acid tocinoic acid (dPen1TA) have been assayed. It was found that dPen1TA and dPen1Pen6TA, both of which have a beta,beta-dimethyl-beta-mercaptopropionic acid in position 1, are strong inhibitors of the uterine activity of oxytocin in vitro (without Mg2+) with pA2 values of 7.1 and 7.8, respectively, whereas dPen6TA with penicillamine in position 6 is a mild agonist.
|
| 3771562 |
Molecular defect of prothrombin Barcelona. Substitution of cysteine for arginine at residue 273 |
None |
J Biol Chem |
Molecular defect of prothrombin Barcelona. Substitution of cysteine for arginine at residue 273
Abstract
- Prothrombin Barcelona has been isolated from a patient with a normal prothrombin antigen level but low prothrombin coagulant activity. The activation of this protein is impaired by the absence of one of the two factor Xa-catalyzed cleavages that normally lead to the formation of thrombin. Prothrombin Barcelona and prothrombin were isolated from patient plasma and normal plasma, respectively, in a single-step, high-yield immunoaffinity purification using conformation-specific antibodies immobilized on Sepharose. After reduction and alkylation, the purified proteins were subjected to trypsin hydrolysis. The resulting peptides were separated by reverse-phase high performance liquid chromatography. Comparison of the peptide maps of prothrombin Barcelona and prothrombin demonstrated that a peptide, identified as fragment 274-287 in prothrombin by automated Edman degradation, was missing in the prothrombin Barcelona digest. In the chromatogram derived from prothrombin Barcelona, an additional peptide was observed. The amino acid sequence of this peptide was Ala-Ile-Glu-Gly-Cys-Thr-Ala-Thr-Ser-Glu-Tyr-Gln-Thr-Phe-Phe-Asn-Pro-Arg, corresponding to residues 269-287 in prothrombin except for the substitution of cysteine for arginine at residue 273. The substitution of cysteine for arginine was confirmed by tryptic digestion of 14C-carboxymethylated prothrombin Barcelona. Edman degradation of fragment 269-287 indicated the association of 14C with the cysteine at residue 273. The replacement of arginine by cysteine at residue 273, adjacent to the known factor Xa cleavage site, precludes normal activation of prothrombin Barcelona by factor Xa and the generation of thrombin.
|
| 3779027 |
Synthesis, characterization, and structural properties of linear and cyclic enkephalin pseudopeptide diastereomers |
None |
Biopolymers |
Synthesis, characterization, and structural properties of linear and cyclic enkephalin pseudopeptide diastereomers
Abstract
|
| 3793372 |
Variability in the backbone conformation of cyclic pentapeptides. Crystal structure of cyclic(Gly-L-Pro-D-Phe-Gly-L-Ala) |
10.1111/j.1399-3011.1986.tb03274.x. |
Int J Pept Protein Res |
Variability in the backbone conformation of cyclic pentapeptides. Crystal structure of cyclic(Gly-L-Pro-D-Phe-Gly-L-Ala)
Abstract
- All the peptide bonds in cyclic(Gly-L-Pro-D-Phe-Gly-L-Ala) are in the trans conformation; however, the peptide bond C'5-N1 is twisted by 19 degrees from planarity (omega 5 = -161 degrees). A Type II beta-turn encompasses the L-Pro-D-Phe residues. Carbonyl oxygens O2, O4 and O5 are directed to the same side of the average plane through the backbone ring and they form hydrogen bonds with N3, N5 and N1, respectively, in adjacent molecules in a stacked column where the adjacent molecules are related by one translational unit. The conformation of the backbone is different from that established in other molecules with the DLDDL chirality sequence. The P21 cell contains two molecules of C21H26N5O5 with a = 4.836(2) A, b = 18.346(8) A, c = 12.464(5) A and beta = 100.05(4) degrees. The R factor for 1382 data with F0 greater than 1 sigma is 7.0%."
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