Synthesis and biological activity of highly active alpha-aza analogues of luliberin. 1978

A S Dutta, and B J Furr, and M B Giles, and B Valcaccia

Analogues of luliberin containing an alpha-azaamino acid in position 6, 9, or 10 (I--XIV) have been synthesized by the solution method of peptide synthesis. Two nonaza analogues, [D-Phe6]- and [D-Ser(But)6,des-Gly-NH2(10),Pro-ethylamide9]luliberin, were also synthesized for comparison. The ovulation-inducing activity of the compounds was evaluated in androgen-sterilized constant-estrus rats. A combination of D-amino acid replacement in position 6 with an azaglycine residue at position 10 resulted in highly active compounds which were superior to the corresponding nonaza analogues. The most active compoungs, [D-Phe6,Azgly10-a1-, [D-Tyr(Me)6,Azgly10]-, and [D-Ser(But)6,Azgly10]luliberin, were about 100 times as potent as luliberin. N-Methylleucine substitution in position 7 in these compounds resulted in decreased activity; [D-Phe6,MeLeu7,Azgly10]- and [D-Tyr(Me)6,MeLeu7,Azgly10]luliberin were only 50 times as active as luliberin. The presence of either an azaproline residue in position 9, an azaphenylalanine or azaglycine residue in positions 6 and 10, or a tert-butyl ether protecting group on the hydroxyl group of the tyrosine residue in position 5 resulted in compounds with significantly reduced biological activity.

UI MeSH Term Description Entries
D007987 Gonadotropin-Releasing Hormone A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND. FSH-Releasing Hormone,GnRH,Gonadoliberin,Gonadorelin,LH-FSH Releasing Hormone,LHRH,Luliberin,Luteinizing Hormone-Releasing Hormone,Cystorelin,Dirigestran,Factrel,Gn-RH,Gonadorelin Acetate,Gonadorelin Hydrochloride,Kryptocur,LFRH,LH-RH,LH-Releasing Hormone,LHFSH Releasing Hormone,LHFSHRH,FSH Releasing Hormone,Gonadotropin Releasing Hormone,LH FSH Releasing Hormone,LH Releasing Hormone,Luteinizing Hormone Releasing Hormone,Releasing Hormone, LHFSH
D010060 Ovulation The discharge of an OVUM from a rupturing follicle in the OVARY. Ovulations
D005260 Female Females
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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