Substrate specificity of an adenohypophyseal endopeptidase capable of hydrolyzing luteinizing hormone-releasing hormone: preferential cleavage of peptide bonds involving the carboxyl terminus of hydrophobic and basic amino acids

Biochemistry ◽  
1982 ◽  
Vol 21 (5) ◽  
pp. 1033-1036 ◽  
Author(s):  
Bernhard Horsthemke ◽  
Karl Bauer
Keyword(s):  
Amino Acids ◽  
Luteinizing Hormone ◽  
Substrate Specificity ◽  
Carboxyl Terminus ◽  
Peptide Bonds ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Basic Amino Acids ◽  
Preferential Cleavage

Antiovulatory Potency and Conformation of an Antagonist of the Luteinizing Hormone-Releasing Hormone Having Six D-Amino Acids

1982 ◽  
Vol 37 (7) ◽  
pp. 872-876 ◽  
Author(s):  
Karl Folkers ◽  
Cyril Y. Bowers ◽  
Frank Momany ◽  
Klaus J. Friebel ◽  
Teresa Kubiak ◽  
...  
Keyword(s):  
Amino Acids ◽  
Luteinizing Hormone ◽  
Conformational Structure ◽  
Design Synthesis ◽  
Luteinizing Hormone Releasing Hormone ◽  
Energy Calculations ◽  
Releasing Hormone ◽  
Routes Of Administration ◽  
Antiovulatory Activity

Abstract [N-Ac-Thr 1 ,D-Phe 2,D-Trp 3,6]-LHRH was the model antagonist of LHRH, which was the basis for tho design, synthesis and bioassay of seven peptides having four, five and six D-amino acids, which resulted from three single, three double, and one triple introductions of D-amino acids in positions 4, 5 and 8 of the model. Only the analog with six D-amino acids, [N-Ac-Thr 1,D-Phe 2 ,D-Trp 3,D-Ser 4, D-Tyr 5 ,D-Trp 6 ,D-Arg 8]-LHRH, had antiovulatory activity which was higher than that of the model antagonist, i.e., 70% antiovulatory activity at 25 μg/rat compared with 50% activity at 50 μg/rat, respectively. Empirical energy calculations gave a conformational structure for [N-Ac-Thr 1,D-Phe 2,D-Trp 3, D-Ser 4,D-Tyr 5,D-Arg 6,D-Arg 8]-LHRH which is similar to that calculated for previous potent antagonists. These results are a basis of new designs of antagonists having D-sub-stituents in up to ten positions toward effective inhibitors of ovulation by the parenteral and oral routes of administration.

The solution conformation of the luteinizing hormone-releasing hormone (LHRH) anti-sense and reversed anti-sense peptides

1990 ◽  
Vol 68 (7) ◽  
pp. 1083-1091
Author(s):  
Albin Otter ◽  
Paul G. Scott ◽  
John M. Stewart ◽  
George Kotovych
Keyword(s):  
Amino Acids ◽  
Luteinizing Hormone ◽  
Two Dimensions ◽  
Helical Conformation ◽  
Solution Conformation ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Fast Exchange ◽  
Helical Turn ◽  
C Nmr

The LHRH anti-sense peptide (Ser1-Arg2-Ala3-Gln4-Ser5-Ile6-Gly7-Pro8-Val9-Leu10) and the inversed sequence, the LHRH inversed anti-sense peptide, have been studied by 1H and 13C NMR in one and two dimensions. The spectroscopic evidence, obtained in CD3OH/H2O (60/40) solution at pH 3.6, indicates that the first four amino acids of the anti-sense peptide form one complete 310-helical turn followed by an extended conformation for the rest of the peptide. On the time-averaged NMR scale the molecules in the 310-helical conformation are in fast exchange with the molecules that are extended throughout (major conformer). The reversed anti-sense peptide exhibits less discernible features. It appears likely that a small percentage of the molecules form a β-turn in the C-terminal four residues. Another β-turn might be located in the Val2-Ile5 fragment. Both turns occur in very minor concentrations only, and therefore it is impossible to define what kind of β-turns are present. Keywords: LHRH anti-sense, inversed anti-sense, conformation, NMR.

Synthesis of a novel class of heteroaromatic amino acids and their use in the preparation of analogs of luteinizing hormone-releasing hormone

1984 ◽  
Vol 27 (3) ◽  
pp. 320-325 ◽  
Author(s):  
John J. Nestor ◽  
Bonnie L. Horner ◽  
Teresa L. Ho ◽  
Gordon H. Jones ◽  
Georgia I. McRae ◽  
...  
Keyword(s):  
Amino Acids ◽  
Luteinizing Hormone ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone

Luteinizing hormone-releasing hormone antagonists containing very hydrophobic amino acids

1984 ◽  
Vol 27 (9) ◽  
pp. 1170-1174 ◽  
Author(s):  
John J. Nestor ◽  
Ram Tahilramani ◽  
Teresa L. Ho ◽  
Georgia I. McRae ◽  
Brian H. Vickery
Keyword(s):  
Amino Acids ◽  
Luteinizing Hormone ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Hydrophobic Amino Acids ◽  
Hormone Antagonists

Antagonists of the Luteinizing Hormone Releasing Hormone with Emphasis on Amino Acids in Position Five

1985 ◽  
Vol 40 (2) ◽  
pp. 313-316 ◽  
Author(s):  
Karl Folkers ◽  
Cyril Y. Bowers ◽  
Liu Yin-Zeng ◽  
Xiao Shao-Bo ◽  
Hong-Ming Shieh ◽  
...  
Keyword(s):  
Amino Acids ◽  
Luteinizing Hormone ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Antiovulatory Activity ◽  
Better Than

Abstract Seventeen analogs of the luteinizing hormone releasing hormone (LHRH) have been synthesized, bioassayed, and compared for antiovulatory activity (AOA) in rats. The emphasis of design was replacement of Tyr5 of LHRH. Position 5 has not been extensively studied. [N-Ac-D-2-Nal1 , D-pClPhe2 , D-3-Pal3 , D-Arg6 , D-Ala10 ]-LHRH was the baseline for new designs. Comparison of the AOA's of the 17 analogs with the baseline revealed the two peptides with Phe5 and 3-Pal5 had equivalent AOA's, and were the best of the 17, and about 45% more potent than the baseline. Analogs with pClPhe5 , oClPhe5 , α-MepClPhe5 , 2-Nal5 , Trp5 , and His5 were less potent than the Phe5 -and 3-Pal5 -analogs. Based on the Phe5 -analog, eight other analogs were synthesized with changes in positions 1, 2, 3 and 7 and although none were better than the baseline, 5/8 showed 20-60% AOA's at 250 ng and revealed optimum positions for new designs.

Effect of N-methyl substitution of the peptide bonds in luteinizing hormone-releasing hormone agonists

1993 ◽  
Vol 36 (3) ◽  
pp. 363-369 ◽  
Author(s):  
Fortuna Haviv ◽  
Timothy D. Fitzpatrick ◽  
Rolf E. Swenson ◽  
Charles J. Nichols ◽  
Nicholas A. Mort ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Peptide Bonds ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Methyl Substitution
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