PT  - JOURNAL ARTICLE
AU  - U Kertscher
AU  - M Brudel
AU  - B Mehlis
AU  - J Sandow
AU  - H Berger
TI  - Pathways of degradation of buserelin by rat kidney membrane.
DP  - 1995 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 709--715
VI  - 273
IP  - 2
4099  - http://jpet.aspetjournals.org/content/273/2/709.short
4100  - http://jpet.aspetjournals.org/content/273/2/709.full
SO  - J Pharmacol Exp Ther1995 May 01; 273
AB  - The pathways of in vitro degradation of the gonadotropin-releasing hormone (GnRH) analog buserelin [pGlu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg- ProNHEt, B1-9] by the rat kidney membrane fraction was investigated using high-performance liquid chromatography for the separation of the peptide products and electrospray mass spectrometry for their identification. The N-terminal peptides B1-4, B1-3, B1-2, C-terminal peptides B3-9, B4-9, B5-9, B6-9, middle sequence B3-4 and the amino acids Trp, Ser and Tyr were found to be formed. However, due to extreme differences in the stability of the peptides toward the battery of membrane enzymes (B1-2, B6-9 > B1-3, B5-9 > B1-9 > B1-4 > B4-9 > B3-9, B3-4), the final products of buserelin degradation were B1-2, B1-3, B5-9, and B6-9 and the amino acids Ser and, corresponding to the formation of B1-2 and B6-9, Trp and Tyr, respectively. The sequences B3-9, B4-9 and B3-4 were clearly detectable only when the inhibitors of aminopeptidases amastatin and bestatin were included in the incubations.(ABSTRACT TRUNCATED AT 250 WORDS)