Abstract
Using mainly 9-fluorenylmethyloxycarbonyl amino acid 2, 4, 5-trichlorophenyl esters in the presence of 1-hydroxybenzotriazole and the solid supportp-alkoxybenzyl alcohol resin, synthesis of luteinizing hormone releasing hormone analogues was carried out with minimal side-chain protection. Catalytic transfer hydrogenation was employed for removal of NO2 and Z-groups from Arg and < Glu respectively avoiding the use of HF and this led to good yields. An aromatic, hydrophilic amino acid, D-(p-hydroxyphenyl) glycine was incorporated into luteinizing hormone releasing hormone molecule along with other modifications. The agonistic as well as antagonistic activities of all the peptides have been studied
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- LHRH:
-
Luteinizing hormone releasing hormone
- SPS:
-
solid phase synthesis
- Fmoc:
-
9-fluorenylmethyloxycarbonyl
- Hpg:
-
(p-hydroxyphenyl)glycine
- CTH:
-
catalytic transfer hydrogenation
- DCC:
-
dicyclohexylcarbodiimide
- HOBt:
-
1-hydroxybenzotriazole
- OTcp:
-
trichlorophenyl esters
- DMF:
-
dimethylformamide
References
Carpino, L. H. and Han, G. Y. (1972)J. Org. Chem.,37, 3404.
Carpino, L. H. and Han, G. Y. (1973)J. Org. Chem.,38,4218.
Chang, C. D., Waki, M., Ahmad, M., Meienhofer, J., Lundell, E. O. and Hang, J. D. (1980)Int. J. Peptide Protein Res.,15, 59.
Channabasavaiah, K. and Stewart, J. (1979)Biochem. Biophys. Res. Commun.,86, 1266.
Erchegui, J., Coy, D. H., Nekola, M. V., Schally, A. V., Mezo, I. and Teplan, I. (1981)Biochem. Biophys. Res. Commun.,100, 915.
Gui-shen Lu,Svetlana, M., James, P. T. and Merrifield, R, B. (1981)J. Org. Chem.,46, 3433.
Kaiser, E., Colescott, R. L., Bossinger, C. D. and Cook, P. I. (1970)Anal. Biochem.,34, 595.
Meienhofer, J., Waki, M., Heiner, E. P., Lambros, T. J., Makofski, R. C. and Chang, C. D. (1979)Int. J. Peptide Protein Res.,13, 35.
Rivier, J. and Vale, W. (1978)Life Sci.,23, 869.
Schally, A. V., (1978)Science,202, 18.
Schally, A. V., Kastin, A. J. and Coy, D. H. (1976)Int. J. Fertil.,21, 1.
Schally, A. V. and Coy, D. H. (1977) inHypothalamic peptide hormones and pituitary regulation (ed. J. C. Porter) (New York: Plenum) p. 99.
Schally, A. V., Arimura, A. and Coy, D. H. (1980)Vitam. Horm.,38, 257.
Sivanandaiah, K. M. and Gurusiddappa, S. (1979)J. Chem. Res., 108.
Sivanandaiah, K. M. and Gurusiddappa, S. (1981)Synthesis,7, 565.
Sivanandaiah, K. M. and Gurusiddappa, S. (1982)Indian J. Chem.,B21, 857.
Sivanandaiah, K. M. and Gurusiddappa, S. (1984)Indian J. Chem.,B23, 372.
Tessier, M., Alberico, F., Pedrose, E., Grandas, A., Eritja, R., Giralt, E., Granier, C. and Van Riet Schoten, J. (1983)Int. J. Peptide Protein Res.,22, 125.
Vale, W., Grant, G., Amoss, M., Blackwell, R. and Guillemin, R. (1972a)Endocrinology,91, 562.
Vale, W., Grant, G., Rivier, J., Monahan, M., Amoss, M., Blackwell, R., Burgus, R. and Guillemin, R. (1972b)Science,176, 933.
Wang, S. S. (1973)J. Am. Chem. Soc.,95, 1328.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sivanandaiah, K.M., Gurusiddappa, S., Gowda, D.C. et al. Improved solid phase synthesis of luteinizing hormone releasing hormone analogues using 9-fluorenylmethyloxycarbonyl amino acid active esters and catalytic transfer hydrogenation with minimal side-chain protection and their biological activities. J Biosci 14, 311–317 (1989). https://doi.org/10.1007/BF02716692
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02716692