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New potent hGH‐RH analogues with increased resistance to enzymatic degradation
Author(s) -
Izdebski Jan,
Witkowska Ewa,
Kunce Danuta,
Orłowska Alicja,
Baranowska Bogusława,
Radzikowska Małgorzata,
Smoluch Marek
Publication year - 2002
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.409
Subject(s) - chemistry , trypsin , peptide , cleavage (geology) , high performance liquid chromatography , enzyme , stereochemistry , derivative (finance) , chromatography , biochemistry , geotechnical engineering , fracture (geology) , engineering , financial economics , economics
Four hGH‐RH analogues containing homoarginine (Har) and/or D ‐Arg were obtained by solid‐phase methodology using Boc‐chemistry. To introduce Har residues, a Lys(Fmoc) protected Lys derivative was incorporated in the appropriate positions (11, 12, 20, 21 or 29); after assembly of the peptide chain the Fmoc group was removed and the peptide‐resin was guanidinylated by treatment with N , N ′‐bis( tert ‐butoxycarbonyl)‐ S ‐methylisothiourea. The peptides were cleaved from the resin by treatment with liquid HF, and the products were purified by RP‐HPLC. The peptides were subjected to digestion by trypsin, and the course of the reaction was followed by HPLC and ESI‐MS. It was found that peptide bonds formed by the carboxyl group of Har are completely stable to trypsin. The course of cleavage at Lys or Arg residues depends on the position of Har in the sequence. All the analogues investigated stimulate the release of GH in rats after subcutaneous administration, and were about 50–100 times as potent as rGH‐RH itself. The analogues had no effect on PRL, LH and FSH levels. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.