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Synthesis, biological activity and resistance to enzymic degradation of luteinizing hormone—releasing hormone analogues modified at position 7
Author(s) -
Hazum E.,
Fridkin M.,
Baram T.,
Koch Y.
Publication year - 1981
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(81)80313-4
Subject(s) - chemistry , hormone , library science , biochemistry , computer science
Luteinizing hormone-releasing hormone (LHRH) can be rapidly degraded by peptidases present in the hypothalamus and the anterior pituitary of the rat [l-4]. A specific endopeptidase has been recognized which initially cleaves the decapeptide pGlu-HisTrp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 at the Gly6-Leu7 bond, yielding the corresponding hexaand tetrapeptide fragments [l-3]. Since LHRHdegrading activity is present both at the site of synthesis and release of LHRH (the hypothalamus) and its site of action (the pituitary),it is possible that these peptidases play a physiological role in controlling the level of the peptide in the body. Investigation of the pattern of biodegradation of the neurohormone may guide the design and the synthesis of stable, long-acting LHRH analogues with possible, valuable clinical applications. We have demonstrated a correlation between the increased biological potencies of some LHRH analogues (substituted at position 6 by D-amino acids) and their resistance to enzymic degradation [5]. Here we have synthesized 3 new LHRH analogues modified at position 7 by hydrophobic amino acids: [Phe7]-LHRH, [Cha7]-LHRH and [cLeu7]-LHRH,and examined their biological activity and their stability to enzymic attack.