Abstract
Des(Pro9,Gly10)-LH-RH ethylamide, des(Pro9,Gly10)-LH-RH butylamide, desGly10-LH-RH 2-aminoethylamide, and desGly10-LH-RH hydrazide were synthesized by a solid-phase method involving cleavage of protected peptide intermediates from their resin support by reaction with ethylamine, butylamine, ethylenediamine, and hydrazine, respectively. In the assay utilizing steroid pretreated, ovariectomized rats, the peptides were found to have the following LH-releasing activities when compared with natural LH-RH: ethylamide, 0.2%; butylamide, 0.1%; 2-aminoethylamide, 2.4%; hydrazide, 12%. DesGly10-LH-RH hydrazide was used as a precursor in the synthesis of desGly10-LH-RH allylamide and desGly10-LH-RH propargylamide by conversion to the azide and reaction with allylamine and propargylamine, respectively. LH and FSH levels were measured over a 4-hr period after subcutaneous injection of these two peptides into immature male rats in order to detect any prolongation of activity. The allylamide analog was quite active, releasing 1.7 times more LH and 1.3 times more FSH than the same dose of LH-RH. The propargylamide analog was considerably less active, exhibiting 50% LH-releasing activity and 64% FSH-releasing activity. Neither peptic e appeared to be longer acting than LH-RH.
| Original language | English |
|---|---|
| Pages (from-to) | 275-277 |
| Number of pages | 3 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 18 |
| Issue number | 3 |
| State | Published - Dec 1 1975 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
Synthesis and biological activity of LH-RH analogs modified at the carboxyl terminus. / Coy, David H.; Coy, Esther J.; Schally, Andrew V; Vilchez-Martinez, Jesus A.
In: Journal of Medicinal Chemistry, Vol. 18, No. 3, 01.12.1975, p. 275-277.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis and biological activity of LH-RH analogs modified at the carboxyl terminus
AU - Coy, David H.
AU - Coy, Esther J.
AU - Schally, Andrew V
AU - Vilchez-Martinez, Jesus A.
PY - 1975/12/1
Y1 - 1975/12/1
N2 - Des(Pro9,Gly10)-LH-RH ethylamide, des(Pro9,Gly10)-LH-RH butylamide, desGly10-LH-RH 2-aminoethylamide, and desGly10-LH-RH hydrazide were synthesized by a solid-phase method involving cleavage of protected peptide intermediates from their resin support by reaction with ethylamine, butylamine, ethylenediamine, and hydrazine, respectively. In the assay utilizing steroid pretreated, ovariectomized rats, the peptides were found to have the following LH-releasing activities when compared with natural LH-RH: ethylamide, 0.2%; butylamide, 0.1%; 2-aminoethylamide, 2.4%; hydrazide, 12%. DesGly10-LH-RH hydrazide was used as a precursor in the synthesis of desGly10-LH-RH allylamide and desGly10-LH-RH propargylamide by conversion to the azide and reaction with allylamine and propargylamine, respectively. LH and FSH levels were measured over a 4-hr period after subcutaneous injection of these two peptides into immature male rats in order to detect any prolongation of activity. The allylamide analog was quite active, releasing 1.7 times more LH and 1.3 times more FSH than the same dose of LH-RH. The propargylamide analog was considerably less active, exhibiting 50% LH-releasing activity and 64% FSH-releasing activity. Neither peptic e appeared to be longer acting than LH-RH.
AB - Des(Pro9,Gly10)-LH-RH ethylamide, des(Pro9,Gly10)-LH-RH butylamide, desGly10-LH-RH 2-aminoethylamide, and desGly10-LH-RH hydrazide were synthesized by a solid-phase method involving cleavage of protected peptide intermediates from their resin support by reaction with ethylamine, butylamine, ethylenediamine, and hydrazine, respectively. In the assay utilizing steroid pretreated, ovariectomized rats, the peptides were found to have the following LH-releasing activities when compared with natural LH-RH: ethylamide, 0.2%; butylamide, 0.1%; 2-aminoethylamide, 2.4%; hydrazide, 12%. DesGly10-LH-RH hydrazide was used as a precursor in the synthesis of desGly10-LH-RH allylamide and desGly10-LH-RH propargylamide by conversion to the azide and reaction with allylamine and propargylamine, respectively. LH and FSH levels were measured over a 4-hr period after subcutaneous injection of these two peptides into immature male rats in order to detect any prolongation of activity. The allylamide analog was quite active, releasing 1.7 times more LH and 1.3 times more FSH than the same dose of LH-RH. The propargylamide analog was considerably less active, exhibiting 50% LH-releasing activity and 64% FSH-releasing activity. Neither peptic e appeared to be longer acting than LH-RH.
UR - http://www.scopus.com/inward/record.url?scp=0016613630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0016613630&partnerID=8YFLogxK
M3 - Article
C2 - 1094115
AN - SCOPUS:0016613630
VL - 18
SP - 275
EP - 277
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 3
ER -