Synthesis of new cyclopeptide analogues of the miuraenamides

2021 ◽  
Vol 18 ◽  
Author(s):  
Sarah Kappler ◽  
Andreas Siebert ◽  
Uli Kazmaier
Keyword(s):  
Natural Products ◽  
Biological Properties ◽  
Amide Bond ◽  
Side Chain ◽  
Aromatic Side Chain ◽  
Highly Active ◽  
C Terminus ◽  
Terminal Amino ◽  
High Cytotoxicity ◽  
Derivatives Of

Introduction: Miuraenamides belong to marine natural compounds with interesting biological properties. Materials and Methods: They initiate polymerization of monomeric actin and therefore show high cytotoxicity by influencing the cytoskeleton. New derivatives of the miuraenamides have been synthesized containing a N-methylated amide bond instead of the more easily hydrolysable ester in the natural products. Results: Incorporation of an aromatic side chain onto the C-terminal amino acid of the tripeptide fragment also led to highly active new miuraenamides. Conclusion: We could show that the ester bond of the natural product miuraenamide can be replaced by an N-methyl amide. The yields in the cyclization step are high and generally much better that with the corresponding esters. On the other hand, the biological activity of the new amide analogs are lower compared to the natural products, but the activity can significantly be increased by incorporation of a p-nitrophenyl group at the C-terminus of the peptide fragment.

scholarly journals Does Cysteine Rule (CysR) Complete the CendR Principle? Increase in Affinity of Peptide Ligands for NRP-1 Through the Presence of N-Terminal Cysteine

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 448 ◽  
Author(s):  
Anna K. Puszko ◽  
Piotr Sosnowski ◽  
Françoise Raynaud ◽  
Olivier Hermine ◽  
Gérard Hopfgartner ◽  
...  
Keyword(s):  
Peptide Ligands ◽  
Side Chain ◽  
Amino Group ◽  
Structure Activity ◽  
C Terminus ◽  
Neuropilin 1 ◽  
Ic50 Value ◽  
N Terminus ◽  
Terminal Amino ◽  
Relationship Of

The structure-activity relationship of branched H-Lys(hArg)-Dab-Dhp-Arg-OH sequence analogues, modified with Cys-Asp or Cys at N-terminal amino acids (Lys, hArg), in VEGF-A165/Neuropilin-1 complex inhibition is presented. The addition of Cys residue led to a 100-fold decrease in the IC50 value, compared to the parent peptide. The change occurred regardless of coupling Cys to the free N-terminal amino group present in the main or the side chain. A few analogues extended by the attachment of Cys at the N-terminus of several potent NRP-1 peptide ligands documented in the literature are also presented. In all studied cases, the enhancement of inhibitory properties after the addition of Cys at the N-terminus is observed. It is particularly evident for the tetrapeptide derived from the C-terminus of VEGF-A165 (KPRR), suggesting that extending the K/RXXK/R motif (CendR) with the Cys moiety can significantly improve affinity to NRP-1 of CendR peptides.

scholarly journals Peptide inhibitors of Streptomycesdd-carboxypeptidases

1973 ◽  
Vol 131 (1) ◽  
pp. 163-171 ◽  
Author(s):  
Manuel Nieto ◽  
Harold R. Perkins ◽  
Mélina Leyh-Bouille ◽  
Jean-Marie Frère ◽  
Jean-Marie Ghuysen
Keyword(s):  
Catalytic Activity ◽  
Experimental Evidence ◽  
Peptide Inhibitors ◽  
Amide Bond ◽  
Side Chain ◽  
Peptide Substrates ◽  
The Third ◽  
C Terminus ◽  
Micro Organisms ◽  
Initial Binding

1. Peptides that inhibit the dd-carboxypeptidases from Streptomyces strains albus G and R61 were synthesized. They are close analogues of the substrates of these enzymes. The enzymes from albus G and R61 strains are in general inhibited by the same peptides, but the enzyme from strain R39 differs considerably. 2. The two C-terminal residues of the peptide substrates and inhibitors appear to be mainly responsible for the initial binding of the substrate to the enzymes from albus G and R61 strains. The side chain in the third residue from the C-terminus seems critical in inducing catalytic activity. 3. Experimental evidence is presented suggesting that the amide bond linking the two C-terminal residues has a cis configuration when bound to the enzymes from strains albus G and R61. 4. The peptide inhibitors are not antibiotics against the same micro-organisms.

scholarly journals Some aliphatic and aromatic amino deriviatives of α-quinoline methiodide.

1931 ◽  
Vol 131 (816) ◽  
pp. 274-274
Keyword(s):  
Physiological Effect ◽  
Side Chain ◽  
Aromatic Side Chain ◽  
Derivatives Of

Many of the amino and acyla.rnino compounds obtained by the condensation of derivatives of α-methyl quinoline with nitroso-acylamines possess active antiseptic and in some cases mild trypanocidal properties. It appeared interesting to examine the physiological effect of substances obtained by attaching a basic aliphatic or aromatic side-chain directly to the α-carbon. of the quinoline nucleus.

scholarly journals Interaction between calmodulin and five different spin-labelled chlorophenothiazines

1986 ◽  
Vol 233 (3) ◽  
pp. 853-857 ◽  
Author(s):  
J L Olivier ◽  
D Rainteau ◽  
G Bereziat ◽  
C Wolf
Keyword(s):  
Ionic Strength ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Side Chain ◽  
Amino Group ◽  
Electrostatic Binding ◽  
Terminal Amino ◽  
Influence Of Ph ◽  
Derivatives Of

The binding to purified calmodulin of five spin-labelled derivatives of chlorophenothiazine was investigated by e.s.r. spectrometry and by the antagonizing potency on the calmodulin-dependent activation of myosin light chain kinase. The results of a comparative study and the influence of pH and ionic strength on the binding support the occurrence of an electrostatic binding involving the terminal amino group of the side-chain of the chlorophenothiazine. These results are discussed in relation to the specificity of the interaction that holds the antipsychotic drug-calmodulin complex together.

scholarly journals Some aliphatic and aromatic amino derivatives of α-quinoline methiodide

1931 ◽  
Vol 108 (755) ◽  
pp. 130-137 ◽  
Keyword(s):  
General Formula ◽  
Direct Action ◽  
Physiological Effect ◽  
Side Chain ◽  
Aromatic Side Chain ◽  
Amino Derivatives ◽  
Derivatives Of

In a series of papers by Browning, Cohen, Ellingworth and Gulbransen it was shown that many of the amino and acylamino compounds obtained by the condensation of derivatives of α-methylquinoline with nitroso-acylamines possess active antiseptic, and in some cases mild trypanocidal properties.These substances have the following general formula in which X represents an amino or acylamino group. X― ―CH : N ― X | N / CH, I It appeared interesting to examine the physiological effect of substances obtained by attaching by means of nitrogen a basic aliphatic or aromatic side-chain directly to the α-carbon of the quinoline nucleus, replacing in this way the above CH group. These substances are in general easily obtained from the methiodide of α-iodoquinoline by the direct action of the base or by using as condensing agent pyridine or piperidine according to the following reaction.

Antibacterial and Cytotoxic Natural and Synthesized Hydroquinones from Sponge Ircinia spinosula

1999 ◽  
Vol 54 (5-6) ◽  
pp. 417-423 ◽  
Author(s):  
Nikos Mihopoulos ◽  
Constantinos Vagias ◽  
Ioanna Chinou ◽  
Christos Roussakis ◽  
Michael Scoullos ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Natural Products ◽  
Antibacterial Effect ◽  
Antibacterial Activities ◽  
Activity Relationship ◽  
Side Chain ◽  
Structure Activity ◽  
Biological Studies ◽  
Wide Range ◽  
Derivatives Of

Abstract In order to check the structure-activity relationship and find more potent derivatives of the natural products 1 and 2 obtained from sponge Ircinia spinosula, a series of oxidation, hydrogenation, acetylation and methylation derivatives was prepared. All compounds (natural and synthetic ones) were screened for their cytotoxic and antibacterial activities. The biological studies showed a wide range of antibacterial activity even though only 2 and 2d showed a moderate cytotoxicity against the clone C98. The oxidation of the hydroquinone to quinone and the hydrogenation of the side-chain increased the antibacterial effect of the molecules.

Chemoselective and orthogonal ligation techniques

1999 ◽  
Author(s):  
James P. Tam ◽  
Y.-A. Lu
Keyword(s):  
Acyl Migration ◽  
Amide Bond ◽  
Side Chain ◽  
Peptide Backbone ◽  
Chemoselective Ligation ◽  
Circular Proteins ◽  
Peptide Dendrimers ◽  
C Terminus ◽  
Reactive Groups ◽  
Peptide Segments

Peptide synthesis through segment ligation of unprotected peptides (total synthesis) and peptides to proteins (semi-synthesis) in aqueous solution is appealingly simple and efficient because protection and activation steps are not required. In addition, this method offers the potential to access a diverse group of macromolecules such as circular proteins, branched peptides, and protein conjugates which are difficult to obtain through conventional approaches using protecting group strategies. Furthermore, the use of unprotected peptide segments overcomes the problem of solubility encountered in the conventional approach to the synthesis of large peptides or proteins in solution. Conceptually, ligation can be approached two ways. In the first approach, a non-amide bond is formed between two peptide segments through a pair of mutually reactive functional groups. Typical methods of non-amide ligation include oxime, hydrazone, and thiazolidine as the coupling linkages. This type of reaction is traditionally referred to as chemoselective ligation. Non-amide ligation is characteristically flexible in joining two segments that result in amino-to-amino end, carboxyl-to-amine or end-to- side chain structures. This flexibility permits synthesis of protein mimetics and branched peptide dendrimers. In the second approach, an amide bond is formed through a two-step reaction sequence involving four functional moieties, two nucleophiles and two electrophiles in the reaction centre. This reaction is usually used for end-to-end coupling between the Cα-moiety of one peptide segment and the Nα-terminus of another peptide segment resulting in a peptide-backbone product. Similar to the non-amide chemoselective ligation, the first step in orthogonal ligation is a capture reaction by a pair of mutually reactive groups. In general, two nucleophiles, a weak-base nucleophile on the side chain and an α-amino, are located at the N-terminus as an N-terminal nucleophile 5 (NTN). The two electrophiles, usually an O-glycol-aldehyde or an S-ester 4, are located at the C-terminus of the another peptide segment. The initial non-amide capture of two segments through the side chain NTN with the O- or S-ester to form a covalent intermediate 6 enables the spontaneous proximity-driven intramolecular acyl transfer to occur. This intramolecular acyl migration achieves orthogonality in amide bond formation 7 between a specific α-amine in the presence of other free α- and ɛ-amines.

Isoform Separation by a Mixed-mode Resin, TOYOPEARL MX-Trp-650M

2018 ◽  
Vol 20 (1) ◽  
pp. 61-64 ◽  
Author(s):  
Tsutomu Arakawa
Keyword(s):  
Mixed Mode ◽  
Chemical Properties ◽  
Side Chain ◽  
Particle Sizes ◽  
Physical And Chemical Properties ◽  
Aromatic Side Chain ◽  
Efficient Separation ◽  
Terminal Amino ◽  
Physical And Chemical ◽  
And Chemical Properties

TOYOPEARL particles are cross-linked hydroxylated methacrylic polymers available in different pore and particle sizes. They are conjugated with different ligands to generate ion-exchange, hydrophobic interaction and affinity resins. They have excellent physical and chemical properties. A mixed-mode resin, TOYOPEARL MX-Trp-650M, is made of this particle with tryptophan conjugated via N-terminal amino group and hence has both hydrophobic/aromatic side chain and carboxyl group. In this review, I will summarize the properties of the TOYOPEARL particles and MX-Trp-650M resin and application of this resin for purification of proteins and in some detail the separation of disulfide (SS)- scrambled oligomers of insulin-like growth factor-1 (IGF-1). For this particular application, the intact IGF-1 was used to examine binding and elution conditions of TOYOSCREEN MX-Trp-650M column. Strong binding was obtained at pH 4.0, at which arginine, but not NaCl, resulted in elution. Both NaCl and arginine resulted in elution at pH 6.5. In addition, a pH gradient from 4.0 to 8.5 was effective. When applied to SS-scrambled IGF-1 oligomers, both pH and arginine gradient exhibited an efficient separation of the oligomers.

Analogues of cholecystokinin methylated in the side chain of carboxyterminal phenylalanine

1991 ◽  
Vol 56 (12) ◽  
pp. 2991-2998 ◽  
Author(s):  
Jan Hlaváček ◽  
Jana Pírková ◽  
Pavel Majer ◽  
Miroslava Žertová ◽  
Lenka Maletínská ◽  
...  
Keyword(s):  
Biological Activity ◽  
Gall Bladder ◽  
Side Chain ◽  
Preparative Hplc ◽  
Aromatic Side Chain ◽  
C Terminus ◽  
Bladder Contraction ◽  
Phenylalanine Residue

In the course of our study on cholecystokinin (CCK) a series of Boc-CCK-7 was synthesized. Their carboxyterminal part was modified by phenylalanine derivatives containing 2 or 4 and 2,6 or 2,4,6 methylated aromatic side-chain. During the synthesis, the racemic phenylalanine derivatives were used and peptides containing either L- or D- methylated phenylalanine were separated using a preparative HPLC. Gall bladder contraction, anorectic, sedative and analgetic bioassays of these analogues revealed that all of them behaved as CCK-8 agonists. While the analogues containing L-form of the methylated phenylalanines had almost the same potency (80% - 130%) in comparison to CCK-8, the presence of the D-form decreased the biological activity of corresponding analogues to 8 – 62% of the CCK-8 potency. These results are in agreement with the suggestion that phenylalanine residue in C-terminus takes part in biological activity transduction only.

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