Solid-phase synthesis and utilization of side-chain reactive unnatural amino acids

p-Toluenesulfonyl-S-benzylcysteinyl-tyrosyl-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteinyl-NG-p-toluenesulfanylarginyl-prolyl-glycineamide (I) and S-benzylcysteinyl-tyrosyl-isoleucyl-glutaminyl-asparaginyl-S-benzylcysteinyl-leucyl-prolyl-glycine amide (III) were prepared by solid phase synthesis. After removal of the protecting groups, closure of the disulfide ring, and purification by continuous free-flow electrophoresis [arginine7, proline8]vasopressin (II) and [leucine7, proline8]oxytocin (IV) were obtained. The antidiuretic effect of II is markedly higher than its pressor effect; IV possesses c. 6% of the uterotonic and c. 10% of the galactogogous effect of oxytocin.

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Comparison of the Potency of 8-L-Arginine, 8-D-Arginine and 8-D-Homoarginine Vasopressin Analogs with Substituted Phenylalanine in Position 2

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19941439 ◽

1994 ◽

Vol 59 (6) ◽

pp. 1439-1450 ◽

Cited By ~ 2

Author(s):

Miroslava Žertová ◽

Jiřina Slaninová ◽

Zdenko Procházka

Keyword(s):

Amino Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Basic Amino Acid ◽

The Other ◽

Side Chain ◽

Inhibitory Potency ◽

Phase Synthesis ◽

Other Hand ◽

Order Of Magnitude

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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Solid phase synthesis of Fmoc N-methyl amino acids: Application of the Fukuyama amine synthesis

Tetrahedron Letters ◽

10.1016/s0040-4039(97)01774-7 ◽

1997 ◽

Vol 38 (42) ◽

pp. 7307-7310 ◽

Cited By ~ 32

Author(s):

Lihu Yang ◽

Kuenley Chiu

Keyword(s):

Amino Acids ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Phase Synthesis

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Solid-Phase Synthesis of Peptides, Peptidomimetics, and Cyclic Peptides Using Traceless Aromatic Side-Chain Tethered Building Blocks

10.3390/ecsoc-4-01893 ◽

2000 ◽

Author(s):

Richard Silverman ◽

Younghee Lee

Keyword(s):

Cyclic Peptides ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Building Blocks ◽

Side Chain ◽

Aromatic Side Chain ◽

Phase Synthesis

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Solid Phase Synthesis of a Somatostatin Amide Analogue Using Acid Labile t-Bumeoc Protection and an Acid Labile Anchor Group

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19921707 ◽

1992 ◽

Vol 57 (8) ◽

pp. 1707-1718

Author(s):

Wolfgang Voelter ◽

Gerhard Breipohl ◽

Chryssa Tzougraki ◽

Eveline Jungfleisch-Turgut

Keyword(s):

Amino Acids ◽

Acetic Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Somatostatin Analogue ◽

Phase Synthesis ◽

Anchor Group ◽

Amide Form ◽

Polystyrene Resin ◽

Acid Labile

The solid phase synthesis of an amidated somatostatin analogue based on the principle of differentiated acidolysis is described. The acid labile and smoothly cleavable t-Bumeoc moiety (1% TFA/DCM) is used for temporary Nα-protection of D- and L-amino acids and [4-[[[9H-fluoren-9-yl-methoxycarbonyl]amino](4-methoxyphenyl)methyl]-2-methylphenoxy]acetic acid, attached to an aminomethylated polystyrene resin is used as acid sensitive linker of the solid carrier which releases the peptide in its amide form by treatment with TFA. Its preparation is described in detail.

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Festphasensynthese von Muramyldipeptiden an isomeren Trialkoxybenzylamin-Harzen / Solid Phase Synthesis of Muramyl Dipeptides on Isomeric Trialkoxybenzylamine Resins

Zeitschrift für Naturforschung B ◽

10.1515/znb-1998-0716 ◽

1998 ◽

Vol 53 (7) ◽

pp. 753-764 ◽

Cited By ~ 1

Author(s):

Hans-Jürgen Kohlbaua ◽

Jochen Tschakert ◽

Raed A. Al-Qawasmeh ◽

Tanveer Ahmad Nizamì ◽

Abdul Malik ◽

...

Keyword(s):

Amino Acids ◽

Trifluoroacetic Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Subsequent Treatment ◽

Phase Synthesis ◽

Merrifield Resin

Abstract New isomeric trialkoxybenzylamine resins are developed coupling phthalimidomethyl-3,5-dimethoxyphenols to the Merrifield resin, followed by subsequent treatment with hydrazine. The generated benzylamine function allows DCC coupling w ith the carboxyl function of amino acids and peptides which are removed as amides after treatment with trifluoroacetic acid. These new trialkoxybenzylamine resins allow expeditious syntheses of peptide amides and glycopeptide amides as is demonstrated for muramyl peptides and analogues.

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