Analogues of human calcitonin

Maier, R.

doi:10.1007/bf02546469

Cited by 3 publications

(1 citation statement)

References 5 publications

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“…For example, the replacement of Leu by Trp did not change the helical content, but significantly reduced the sCT activity [24]. Furthermore, the substitution of aromatic residues by Leu residues, which was expected to stabilize and lengthen the helical structure, did not affect the helical content and actually enhanced the activity by the factor of 15-20 in hCT [25]. This could be attributed to steric interactions between the ligand and receptor involving bulky aromatic rings.…”

Section: Discussionmentioning

confidence: 82%

Conformational analysis of elcatonin in solution

Ogawa¹,

Nishimura²,

Doi³

et al. 1994

European Journal of Biochemistry

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The conformational characteristics of elcatonin, an analogue of eel calcitonin having a disulfide bond Cysl-Cys7 replaced by an ethylene linkage between residues 1 and 7, have been analyzed in aqueous trifluoroethanol solutions. Circular dichroic spectra of elcatonin and eel calcitonin itself reveal the presence of a-helices at trifluoroethanol concentrations above 15 %. The spectral changes caused by the trifluoroethanol content of the solutions are interesting. An isosbetic point is detected for eel calcitonin indicating that a conformational transition occurs between two states, namely a-helical and random coil states. On the other hand, the CD curves of elcatonin at less than 15% trifluoroethanol deviate from the isosbetic point while those at higher concentration are similar to those of eCT. This can probably be attributed to the third element of the ordered structure of elcatonin which is formed in 15% trifluoroethanol.The solution conformation of elcatonin in a mixture of 60% water and 40% trifluoroethanol has been determined by the combined use of 'H-NMR spectroscopy and distance geometry calculations. The conformation is characterized by an amphiphilic a-helix between Thr6 and Thr21, which extends into the constrained cyclic portion of the molecule to Thr6. The third structural element of elcatonin found in the CD analysis is detected by some turn structures in the region between residue 1 and Ser5 in the calculated structure.Calcitonin (CT) in many vertebrate species is one of the calcium-regulating peptide hormones which mediates a lowering of serum calcium in response to elevated levels of calcium. The peptide is secreted by the parafollicular or C cells located in the thyroid glands of mammals and by the ultimobranchial gland in lower animals. The amino acid sequences available for several calcitonins reveal three common features: (a) a chain length of 32 amino acid residues, (b) a disulfide bridge between Cys residues at positions 1 and 7 in the N-terminal portion, and (c) a proline amide residue at the C terminus. The physiology and pharmacology of calcitonin have been reviewed by Azria [l].The secondary structure of calcitonins has attracted attention because previous attempts to relate their activity to certain residues or to certain sequence fragments have failed; it is now thought that the overall shape and size of the molecule are more important for the expression of biological activity. In spite of considerable differences in the sequences of calcitonins, sequences between residues 8 and 22 have regularly spaced hydrophobic residues, indicating a possible propensity for amphiphilic a-helical structures [ 2 ] . Although circular dichroic (CD) studies of calcitonins in water show no ~ Correspondence to Y. Kobayashi, Institute for Protein Research, Osaka University, Suita Osaka, Japan, 565Abbreviations. CT, calcitonin; hCT, human calcitonin; sCT, salmon calcitonin; MeOH, methanol; eCT, eel calcitonin; Asu, aminosuberic acid; DQF-COSY, double-quantum-filtered shiftcorrelated spectroscopy; HOHAHA...

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Section: Discussionmentioning

confidence: 82%

Conformational analysis of elcatonin in solution

Ogawa¹,

Nishimura²,

Doi³

et al. 1994

European Journal of Biochemistry

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Calcitonin: A Minireview

Basava¹

1994

Peptides

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Development of Transgenic Mice Expressing Calcitonin as a Beta-lactoglobulin Fusion Protein in Mammary Gland

et al. 2005

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Expression of foreign proteins in mammalian milk is becoming a widespread strategy for high-level production of recombinant pharmaceuticals, especially those with the most complex post-translational modifications. A milk-specific ovine beta-lactoglobulin (oBLG) promoter was used to drive expression of recombinant calcitonin in mouse milk. A gene construct was generated, consisting of 10.7 kbp of the oBLG gene including its promoter and 3' flanking region with the calcitonin coding sequences inserted in-frame into the oBLG fifth exon. After microinjection, six founder mice transmitted the transgene to their progeny. RT-PCR confirmed mammary-gland specific expression of recombinant mRNA in most transgenic mice and Western blot analysis confirmed expression of chimeric protein. Calcitonin can thus be expressed under the oBLG promoter and regulatory elements in a mammary-gland specific manner.

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Analogues of human calcitonin

Cited by 3 publications

References 5 publications

Conformational analysis of elcatonin in solution

Conformational analysis of elcatonin in solution

Calcitonin: A Minireview

Development of Transgenic Mice Expressing Calcitonin as a Beta-lactoglobulin Fusion Protein in Mammary Gland

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