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  • 1
    ISSN: 1573-4943
    Keywords: Oxytocin ; analogues ; conformational constraint ; conformation ; circular dichioism ; oxytocin antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The analogues of oxytocin and [1-penicillamine]oxytocin, containing a cycloleucine (Cle) residue in position 2 or 8, were investigated by means of circular dichroism measurements in different solvents, and the results examined in terms of their biological activities. A cycloleucine residue in position 2 substantially reduces the free conformational space of the hormone 20-membered ring moiety (including the disulfide group), and stabilizes a conformation which is close to one of the possible conformations of oxytocin and involves a β-turn. In position 8, the Cle residue affects the conformation of the Tyr2 side chain, apparently forcing it away from the space above the 20-membered disulfide ring. However, it does not appear that the Cle residue has any significant effect on the overall backbone conformation of the hormone. The steric effect of the penicillamine residue in position 1 on the conformation of the disulfide group and Tyr2 side chain from previous investigations is further confirmed. The synthesis and biological potency of [1-penicillamine, 8-cycloleucine]oxytocin is described. This analogue exhibits a strong inhibitory effect on the uterotonic activity of oxytocinin vitro. It also inhibited the vasopressor response to vasopressin.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    International journal of peptide research and therapeutics 7 (2000), S. 85-92 
    ISSN: 1573-3904
    Keywords: GnRH peptides ; Neobellieria bullata ; peptide synthesis ; reproduction ; solid phase synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Mammal, 125I-mammal, salmon, chicken I and II GnRHs and three fragments of mammal GnRH were synthesized and their effect on oogenesis in the flesh fly Neobellieria(formerly Sarcophaga) bullata (Diptera) was investigated. The peptides were prepared by the Merrifield solid phase synthesis on polystyrene/divinylbenzene polymer using the Nα-Boc strategy in DMF and were purified by preparative RP-HPLC in a gradient of water-MeOH. From the peptides assayed, only mammal GnRH and two of its carboxy-terminus truncated analogs remarkably affected the processes of egg development in ovarioles, causing changes in the follicular epithelium, proliferation of its nuclei and cell division towards the inner part of the egg chamber. The process led to the occurrence of multinuclear follicular epithelium which finally filled up almost the whole egg chamber and then it degenerated. The inability of GnRH of other animal species to evoke the changes in the egg development establishes the question of primary structures of GnRH responsible for these biological effects. The identityof sequences of GnRHs from position 1 up to 6 (with the exception of chicken GnRH II) points to functionality of amino acids located in positions 7 and 8 of the peptide chain. The radioactivity of the 125I-labelled mammal GnRH with maintained oostatic activity and its receptor competition with the non-labelled mammal GnRH were measured in selected insect organs and exhibited different residual values according to the organ and the time after applicationof the peptide. A transfer of the radioactivity into the next (F1) generation was also observed.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0173-0835
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Two carrier-free electrophoretic separation methods, capillary zone electrophoresis (CZE) and continuous free-flow zone electrophoresis (FFZE), have been applied to both microanalysis at the nanogram level and preparative fractionation, with a throughput of 30 mg/h, of synthetic growth hormone releasing peptide (GHRP). A crude product of GHRP, a hexapeptide with the sequence His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, synthesized by the solid phase methodology, was desalted and analyzed by CZE. Based on the results of analytical CZE the separation was converted into a preparative purification procedure by continuous FFZE, employing the same separation medium (0.5 mol/L acetic acid, pH 2.6). The purity of peptide frcttions obtained by FFZE was reevaluated by CZE. The combination of these two techniques proved to be a valuable tool for both peptide analysis and peptide purification. A close correalation of CZE and FFZE, resulting from the fact that both methods are based on the same separation principle (zone electrophoresis) and that both are performed in a free solution of the same composition, was confirmed. However, when transforming data from CZE to FFZE, the different electroosmotic flow, temperature and electric field intensity in the capillary and in the flow-through cell, respectively, have to be taken into account and corresponding corrections have to be made.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Computational Chemistry 12 (1991), S. 829-838 
    ISSN: 0192-8651
    Keywords: Computational Chemistry and Molecular Modeling ; Biochemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: ϕ - ψ maps have been calculated by the MM2(87) potential for the Nα-acetyl derivatives of Gly, Ala, Val, and Tle methylamides and their Nα-methyl substituted derivatives to interpret the 1H NMR and CD spectra of these compounds. From the critical examination of the available theoretical and experimental evidence it follows that in the series of Nα unsubstituted Ala, Val, and Tle derivatives the importance of the second lowest energy conformation (C5) is increased and that eventually it becomes the lowest energy conformation instead of C7eq. With the Nα-methyl substituted Ala and Val derivatives, the lowest energy conformation seems to be C7eq. Performance of MM2(87) was tested for the ϕ - ψ map of the Ala derivative by comparing it with other theoretical data available in the literature.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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