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

An analysis of the uterotonic potencies of all analogs having substituted L- or D-tyrosine or -phenylalanine in position 2 and L-arginine, D-arginine or D-homoarginine in position 8 was made. The series of analogs already published was completed by the solid phase synthesis of ten new analogs having L- or D-Phe, L- or D-Phe(2-Et), L- or D-Phe(2,4,6-triMe) or D-Tyr(Me) in position 2 and either L- or D-arginine in position 8. All newly synthesized analogs were found to be uterotonic inhibitors. Deamination increases both the agonistic and antagonistic potency. In the case of phenylalanine analogs the change of configuration from L to D in position 2 enhances the uterotonic inhibition for more than 1 order of magnitude. The L to D change in position 8 enhances the inhibitory potency negligibly. Prolongation of the side chain of the D-basic amino acid in position 8 seems to decrease slightly the inhibitory potency if there is L-substituted amino acid in position 2. On the other hand there is a tendency to the increase of the inhibitory potency if there is D-substituted amino acid in position 2.

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Synthesis and biological properties of vasopressin analogues containing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19901099 ◽

1990 ◽

Vol 55 (4) ◽

pp. 1099-1105 ◽

Cited By ~ 6

Author(s):

Zdenko Procházka ◽

Juris E. Ancans ◽

Jiřina Slaninová ◽

Alena Machová ◽

Tomislav Barth ◽

...

Keyword(s):

Amino Acid ◽

Carboxylic Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Biological Activities ◽

Biological Properties ◽

Phase Synthesis ◽

Aromatic Residues ◽

Synthesis Methodology ◽

Vasopressin Analogues

Solid phase synthesis methodology on a benzhydrylamine resin was used for the synthesis of three analogues of vasopressin with the non-coded amino acid, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), in the position 2 ([Tic2, Lys8]VP (I)) and in the position 3 ([Tic3, Lys8]VP (II)). The analogue containing only one Tic in place of both aromatic residues was also isolated (des-Tyr2-[Tic3, Lys8]VP (III)). The biological activities of all analogues were negligible.

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Solid-Phase Synthesis with Attachment of Peptide to Resin through an Amino Acid Side Chain: [8-Lysine]-Vasopressin

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.68.5.1006 ◽

1971 ◽

Vol 68 (5) ◽

pp. 1006-1009 ◽

Cited By ~ 8

Author(s):

J. Meienhofer ◽

A. Trzeciak

Keyword(s):

Amino Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Side Chain ◽

Amino Acid Side Chain ◽

Phase Synthesis ◽

Lysine Vasopressin

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Traceless Solid-Phase Synthesis of Chiral 3-Arylβ-Amino Acid Containing Peptides Using a Side-Chain-Tetheredβ-Amino Acid Building Block

Organic Letters ◽

10.1021/ol9912480 ◽

2000 ◽

Vol 2 (3) ◽

pp. 303-306 ◽

Cited By ~ 23

Author(s):

Younghee Lee ◽

Richard B. Silverman

Keyword(s):

Amino Acid ◽

Building Block ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Side Chain ◽

Phase Synthesis

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Oxytocin analogues with non-coded amino acid residues in position 8: [8-Neopentylglycine]oxytocin and [8-cycloleucine]oxytocin

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19872317 ◽

1987 ◽

Vol 52 (9) ◽

pp. 2317-2325 ◽

Cited By ~ 5

Author(s):

Jan Hlaváček ◽

Jan Pospíšek ◽

Jiřina Slaninová ◽

Walter Y. Chan ◽

Victor J. Hruby

Keyword(s):

Amino Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

The Other ◽

Amino Acid Residues ◽

Phase Synthesis ◽

Other Hand ◽

Fragment Condensation

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

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