S and C glycopeptide derivatives of an LH-RH agonist

Katja Michael; Valentin Wittmann; Wolfgang König; Jürgen Sandow; Horst Kessler

doi:10.1111/j.1399-3011.1996.tb01107.x

S and C glycopeptide derivatives of an LH-RH agonist

Katja Michael, Valentin Wittmann, Wolfgang König, Jürgen Sandow, Horst Kessler

TUM Emeriti of Excellence

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

The S- and C-glycosylated nonapeptides 1 and 2 were synthesized as analogs of the non-glycosylated LH-RH agonist buserelin (pGlu-His-Trp-Ser-Tyr-D-Ser(fBu)-Leu-Arg-Pro-NHEt) by segment condensation in solution. 1 and 2 differ from this peptide in the amino acid in position 6. In the first case (1), Dserine (/Bu) is substituted by D-cysteine carrying a rhamnosyl residue, in the second case (2) D-alanine carrying a galactosyl moiety bound as C-glycoside is incorporated. The bioactivity of both glycopeptides as fertility drugs was determined from the dose dependent LH release in male rats. Additionally, in female rats the ovulation rate was assessed. As a result the analog 1 exhibits a similar biological activity as buserelin while analog 2 shows about 25% of this potency. Compared to buserelin the solubility of the analogs 1 and 2 in aqueous buffer is improved by more than two orders of magnitude due to the carbohydrate moieties.

Original language	English
Pages (from-to)	59-70
Number of pages	12
Journal	International Journal of Peptide and Protein Research
Volume	48
Issue number	1
DOIs	https://doi.org/10.1111/j.1399-3011.1996.tb01107.x
State	Published - 1996

Keywords

C-glycosides
Glycopeptides
Gonadotropin release
Lh-rh agonists
Synthesis
Thioglycosides

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10.1111/j.1399-3011.1996.tb01107.x

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title = "S and C glycopeptide derivatives of an LH-RH agonist",

abstract = "The S- and C-glycosylated nonapeptides 1 and 2 were synthesized as analogs of the non-glycosylated LH-RH agonist buserelin (pGlu-His-Trp-Ser-Tyr-D-Ser(fBu)-Leu-Arg-Pro-NHEt) by segment condensation in solution. 1 and 2 differ from this peptide in the amino acid in position 6. In the first case (1), Dserine (/Bu) is substituted by D-cysteine carrying a rhamnosyl residue, in the second case (2) D-alanine carrying a galactosyl moiety bound as C-glycoside is incorporated. The bioactivity of both glycopeptides as fertility drugs was determined from the dose dependent LH release in male rats. Additionally, in female rats the ovulation rate was assessed. As a result the analog 1 exhibits a similar biological activity as buserelin while analog 2 shows about 25% of this potency. Compared to buserelin the solubility of the analogs 1 and 2 in aqueous buffer is improved by more than two orders of magnitude due to the carbohydrate moieties.",

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author = "Katja Michael and Valentin Wittmann and Wolfgang K{\"o}nig and J{\"u}rgen Sandow and Horst Kessler",

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T1 - S and C glycopeptide derivatives of an LH-RH agonist

AU - Michael, Katja

AU - Wittmann, Valentin

AU - König, Wolfgang

AU - Sandow, Jürgen

AU - Kessler, Horst

PY - 1996

Y1 - 1996

N2 - The S- and C-glycosylated nonapeptides 1 and 2 were synthesized as analogs of the non-glycosylated LH-RH agonist buserelin (pGlu-His-Trp-Ser-Tyr-D-Ser(fBu)-Leu-Arg-Pro-NHEt) by segment condensation in solution. 1 and 2 differ from this peptide in the amino acid in position 6. In the first case (1), Dserine (/Bu) is substituted by D-cysteine carrying a rhamnosyl residue, in the second case (2) D-alanine carrying a galactosyl moiety bound as C-glycoside is incorporated. The bioactivity of both glycopeptides as fertility drugs was determined from the dose dependent LH release in male rats. Additionally, in female rats the ovulation rate was assessed. As a result the analog 1 exhibits a similar biological activity as buserelin while analog 2 shows about 25% of this potency. Compared to buserelin the solubility of the analogs 1 and 2 in aqueous buffer is improved by more than two orders of magnitude due to the carbohydrate moieties.

AB - The S- and C-glycosylated nonapeptides 1 and 2 were synthesized as analogs of the non-glycosylated LH-RH agonist buserelin (pGlu-His-Trp-Ser-Tyr-D-Ser(fBu)-Leu-Arg-Pro-NHEt) by segment condensation in solution. 1 and 2 differ from this peptide in the amino acid in position 6. In the first case (1), Dserine (/Bu) is substituted by D-cysteine carrying a rhamnosyl residue, in the second case (2) D-alanine carrying a galactosyl moiety bound as C-glycoside is incorporated. The bioactivity of both glycopeptides as fertility drugs was determined from the dose dependent LH release in male rats. Additionally, in female rats the ovulation rate was assessed. As a result the analog 1 exhibits a similar biological activity as buserelin while analog 2 shows about 25% of this potency. Compared to buserelin the solubility of the analogs 1 and 2 in aqueous buffer is improved by more than two orders of magnitude due to the carbohydrate moieties.

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KW - Glycopeptides

KW - Gonadotropin release

KW - Lh-rh agonists

KW - Synthesis

KW - Thioglycosides

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S and C glycopeptide derivatives of an LH-RH agonist

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Keywords

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