Synthese des «Thyrotropin‐releasing» Hormons (TRH) (Schaf) und verwandter Peptide

Gillessen, Dieter; Lergier, W.; Studer, R. O.; Félix, Arthur

doi:10.1002/hlca.19700530107

Cited by 69 publications

(17 citation statements)

References 25 publications

(9 reference statements)

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“…Synthetic TRF and its analogues have been prepared, and structure-activity relationships studied by both of the above groups (9,(12)(13)(14) and by other workers (15)(16)(17). Natural and synthetic TRF is active in the mouse (14,16,18,19), rat (20), and man (16,17,(21)(22)(23)(24) (25); mean age 13 yr 7 months; group III, 9 patients (8 males, 1 female) with multiple anterior pituitary hormone deficiencies, including deficient TSH, and no demonstrable intracranial mass; mean age 15 yr 8 months.…”

Section: Introductionmentioning

confidence: 99%

Effect of thyrotropin-releasing factor on serum thyroid-stimulating hormone

Costom¹,

Grumbach²,

Kaplan³

1971

J. Clin. Invest.

125

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Section: Introductionmentioning

confidence: 99%

Effect of thyrotropin-releasing factor on serum thyroid-stimulating hormone

Costom¹,

Grumbach²,

Kaplan³

1971

J. Clin. Invest.

125

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“…Following the demonstration that the major product of this reaction was PCA-His-Pro-OH, this com pound which has a specific activity of 10 TRF U/mg was studied; this was followed by experiments using PCA-His-Pro-OMe (20,000 TRF U/mg) and PCA-His-Pro-NH2 (45,000 TRF U/mg) prepared in our laboratory with PCA-His-Pro-OH as starting material [3,5], PCA-His-Pro-NHo has been subsequently shown to be the structure of natural ovine [2] and porcine [13] TRF. The dipeptide PCA-His-OMe (no TRF activity) was prepared in our laboratories by the method of Gillessen et al [7].…”

Section: Trf O F Natural Originmentioning

confidence: 99%

In vitro Plasma Inactivation of Thyrotropin Releasing Factor (TRF) and Related Peptides. Its Inhibition by Various Means and by the Synthetic Dipeptide PCA-His-OME

Vale¹,

Burgus²,

Dunn³

et al. 1971

Horm Res Paediatr

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Incubation in vitro of natural (ovine) or synthetic TRF (PCA-His-Pro-NH₂) with rat blood, plasma, or reconstituted lyophilized serum destroys the biological activity. Inactivation of TRF by normal plasma takes place at 0 °C but at a slower rate than at 37 °C. Plasma obtained from rats several weeks after hypophysectomy and/ or hypophysectomy + thyroidectomy inactivates TRF. TRF activity is not recovered from TRF incubated in plasma when the incubate is treated with NaCl (4 m), ethanol (80% v/v) or HCl (to pH 1). Plasma inactivation of TRF is completely prevented by pretreatment of the plasma with ethanol (80% v/v); heating of plasma at 65 °C for 15 min also destroys the ability of plasma to inactivate TRF. The data reported are consistent with the hypothesis that plasma contains an enzyme (s) which destroys the activity of TRF. Plasma was also found to destroy the biological activity of PCA-His-Pro-OMe and PCA-His-Pro-OH (2 synthetic tripeptides with TRF activity). The biological activity of PCA-His-Pro-OH is destroyed in vitro at a slower rate by plasma than that of PCA-His-Pro-NH₂ or natural TRF. Addition of the dipeptide analogue of TRF, PCA-His-OMe, prevents in vitro the inactivation of TRF by plasma.

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“…This coinpoiintl is easier t o purify by crystallization than Boc-glutamic acid [15 1. 4. Preparation of Boc-L-proline 1iv:ked fo the resin, I?.…”

Section: Preparatiovl O J Boc-l-prolzne Boc-l-glutamic Acid and Boc-mentioning

confidence: 99%

An Efficient Synthesis of Thyrotropin Releasing Hormone (TRH)

Rivaille¹,

Milhaud²

1971

Helvetica Chimica Acta

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Sz~rnmary.A convenient and simple synthesis of L-pyroglutamyl-L-histidyl-L-prolinamide is descril~cd. Two pathways using the solid phase tcchnique have led to the pure tripeptide.Thyrotropin releasing hormone (TRH) was isolated from porcine hypothalamus by Schally et al. [l] and from ovine hypothalamus by Guillemin et al. [ Z ] , and proved to be identical with r*-pyroglutamyl-L-histidyl-L-prolinaniide [3]. A classical synthesis of this tripeptide was reported recently j4] ; the solid phase technique 1 5 1 used here gives better yields, is simpler and quicker.The following reaction scheme was used. t-Butyloxycarbonyl (Boc) is introduced in proline, glutamic acid or glutamine as the amine protecting group j6] using Bocazide at constant alcaline pH. The purity of the Boc-aminoacids was checked by measuring the rotation and by thin-layer chromatography. The histidine imidazole group was protected with o,p-dinitrophenyl before condensation, as selective removal of this group can easily be performed by thiolysis at pH 8 [7].Protected histidine was reacted with proline linked on the chloromethylresin in the presence of dicyclohexyl-carbodiimide (Dcc). The glutamyl residue was introduced in two ways: (A) Boc-pyroglutamic acid was condensed in the presence of Dcc; (B) Boc-glutam.ine dinitrophenylester j 81 was reacted with the dipeptide linked to the resin in dimeth:ylformaniide. The tripeptide was split from the resin by aminolysis 191, the imidazole -protecting group removed, and the glutamine converted into pyroglutamic acid by boiling acetic acid [lo].The tripept.ide was purified by Sepliadex G10 filtration followed by silica-gel chromatography. The pure material did not react with ninhydrin, as could be anticipated due to the presence of prolinamide and pyroglutamic acid. After silica-gel thin layer chromatography in several solvant systems [ll], the product gave a single spot when detected with Pauly's reagent. The optical rotation was of the order of the one published 141. After acid hydrolysis, the three initial aminoacids could be detected by spraying the thin layer chromatoplaque with ninhydrin.

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Synthese des «Thyrotropin‐releasing» Hormons (TRH) (Schaf) und verwandter Peptide

Cited by 69 publications

References 25 publications

Effect of thyrotropin-releasing factor on serum thyroid-stimulating hormone

Effect of thyrotropin-releasing factor on serum thyroid-stimulating hormone

In vitro Plasma Inactivation of Thyrotropin Releasing Factor (TRF) and Related Peptides. Its Inhibition by Various Means and by the Synthetic Dipeptide PCA-His-OME

An Efficient Synthesis of Thyrotropin Releasing Hormone (TRH)

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