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.

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.

Transforming growth factor alpha: an aromatic side chain at position 38 is essential for biological activity

1989 ◽  
Vol 9 (2) ◽  
pp. 860-864
Author(s):  
E Lazar ◽  
E Vicenzi ◽  
E Van Obberghen-Schilling ◽  
B Wolff ◽  
S Dalton ◽  
...  
Keyword(s):  
Biological Activity ◽  
Growth Factor ◽  
Disulfide Bonds ◽  
Transforming Growth Factor ◽  
Site Directed Mutagenesis ◽  
Side Chain ◽  
Transforming Growth Factor Alpha ◽  
Aromatic Side Chain ◽  
Factor Alpha ◽  
Alpha Gene

Site-directed mutagenesis has been performed in the human transforming growth factor alpha gene. When tyrosine 38 is mutated into phenylalanine or tryptophane, biological activity is retained. In contrast, other alterations between cysteine 34 and cysteine 43 and disruption of disulfide bonds 8 to 21 and 34 to 43 resulted in loss of activities. The presence of an aromatic side chain at position 38 of transforming growth factor alpha seems to be essential for its activity.

scholarly journals Transforming growth factor alpha: an aromatic side chain at position 38 is essential for biological activity.

1989 ◽  
Vol 9 (2) ◽  
pp. 860-864 ◽  
Author(s):  
E Lazar ◽  
E Vicenzi ◽  
E Van Obberghen-Schilling ◽  
B Wolff ◽  
S Dalton ◽  
...  
Keyword(s):  
Biological Activity ◽  
Growth Factor ◽  
Disulfide Bonds ◽  
Transforming Growth Factor ◽  
Site Directed Mutagenesis ◽  
Side Chain ◽  
Transforming Growth Factor Alpha ◽  
Aromatic Side Chain ◽  
Factor Alpha ◽  
Alpha Gene

Site-directed mutagenesis has been performed in the human transforming growth factor alpha gene. When tyrosine 38 is mutated into phenylalanine or tryptophane, biological activity is retained. In contrast, other alterations between cysteine 34 and cysteine 43 and disruption of disulfide bonds 8 to 21 and 34 to 43 resulted in loss of activities. The presence of an aromatic side chain at position 38 of transforming growth factor alpha seems to be essential for its activity.

Structural relationships in the two-zinc insulin hexamer

1979 ◽  
Vol 57 (6) ◽  
pp. 469-479 ◽  
Author(s):  
E. J. Dodson ◽  
G. G. Dodson ◽  
D. C. Hodgkin ◽  
C. D. Reynolds
Keyword(s):  
Crystal Structure ◽  
Biological Activity ◽  
Main Chain ◽  
Side Chain ◽  
C Terminus ◽  
Structural Relationships ◽  
N Terminus ◽  
Independent Molecules ◽  
A Chain ◽  
Resolution Data

The refinement of the crystal structure of two-Zn pig insulin using 1.5-Å (1 Å = 0.1 nm) resolution data by Fourier and fast Fourier least-squares methods allows us to make detailed comparisons between the two independent molecules present in the two-Zn insulin dimer and to describe their interactions in the monomer, dimer, and hexamer. The main chain structures for the two molecules agree well except at the N terminus of the A chain and the C terminus of the B chain. The residues along the line of the local two-fold axes, apart from theB25 side chain, conform extremely closely to the two-fold symmetry, although the discrepancies are much more apparent away from this axis. The ability of the insulin molecule to adopt different conformations may be an important factor in the expression of its biological activity.

scholarly journals The semisynthesis of fragments corresponding to residues 66-104 of horse heart cytochrome c

1979 ◽  
Vol 179 (1) ◽  
pp. 169-182 ◽  
Author(s):  
C J Wallace ◽  
R E Offord
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Cytochrome C ◽  
Amino Acid Sequences ◽  
Side Chain ◽  
Horse Heart Cytochrome ◽  
Natural Sequence ◽  
C Terminus ◽  
N Terminus ◽  
Horse Heart Cytochrome C

We describe the N epsilon-acetimidylation of horse heart cytochrome c with retention of biological activity, the cleavage of the modified protein by CNBr, the separation of the fragments, and their further side-chain protection. We describe the manipulation of the amino acid sequences of the fragments by stepwise semisynthetic methods. We have prepared fragments corresponding to residues 66-78 and 66-79 of the protein, as well as the [Asp66] analogue of fragment 66-79. We have prepared the natural sequence and the [o-fluoro-Phe82] analogue of the fragment corresponding to residues 81-104 of the protein, and the [N epsilon-trifluoroacetyl-Lys79], the [N epsilon-dinitrophenyl-Lys79] and the [S-acetamidomethyl-Cys79] analogues of fragment 79-104, and the [N epsilon-Cbz-Lys81] analogue of fragment 80-104. We have coupled back the fragments of natural sequence to form a semisynthetic fragment corresponding to residues 66-104 of the protein. Modified fragments were also coupled to give analogues of the 66-104-residue sequence. In every case the homoserine residue representing methionine-80 was removed from the C-terminus of the 66-80-residue fragment and replaced by methionine on the N-terminus of the 81-104 residue fragment during the preparation of the fragments for coupling. The semisynthetic fragments are ready for specific deprotection and further coupling. We have coupled one such fragment to the (1-65)-peptide to produce semisynthetic [Hse65]cytochrome c. The product has satisfactory characteristics on chemical analysis, and on assay of its biological activity.

Synthesis and biological properties of cholecystokinin heptapeptide analogues containing D- and L-forms of tert-leucine or neopentylglycine in position 5

1991 ◽  
Vol 56 (10) ◽  
pp. 2209-2217 ◽  
Author(s):  
Jan Hlaváček ◽  
Jana Pírková ◽  
Jan Pospíšek ◽  
Jiřina Slaninová ◽  
Lenka Maletínská
Keyword(s):  
Gall Bladder ◽  
Solid Phase ◽  
Biological Activities ◽  
Biological Properties ◽  
Phase Synthesis ◽  
Structural Modifications ◽  
Bladder Contraction ◽  
Anorectic Effect ◽  
Carboxy Terminal ◽  
Anorectic Activity

Using solution or solid-phase synthesis we prepared the cholecystokinin fragment Boc-CCK-7 (Boc-Tyr-(SO3-.Na+)-Met-Gly-Trp-Met-Asp-PheNH2) and its four analogues in which the methionine moiety (Met) in the carboxy-terminal part is replaced by tert-leucine (Tle) or neopentylglycine (Neo) residue or D-enantiomers of these non-coded amino acids. These structural modifications led to reduction of the studied biological activities (gall bladder contraction, anorectic activity, analgetic and sedation activity) of all prepared analogues except Boc[Neo5]-CCK-7 which, being less analgetically active, retains full gall bladder and sedation activity of CCK-8. Moreover, its anorectic activity is substantially higher (400%). This analogue is very interesting particularly for its selectively increased (4x) anorectic effect compared with that of CCK-8.

scholarly journals Synthesis and Biological Activity of Brassinosteroid Analogues with a Nitrogen-Containing Side Chain

2020 ◽  
Vol 22 (1) ◽  
pp. 155
Author(s):  
Mikhail V. Diachkov ◽  
Karoll Ferrer ◽  
Jana Oklestkova ◽  
Lucie Rarova ◽  
Vaclav Bazgier ◽  
...  
Keyword(s):  
Biological Activity ◽  
Functional Groups ◽  
Side Chain ◽  
Biotic And Abiotic Stresses ◽  
Short Side ◽  
Arabidopsis Root ◽  
Physiological Processes ◽  
Growth Promoting ◽  
The Impact ◽  
Brassinosteroid Analogues

Brassinosteroids are a class of plant hormones that regulate a broad range of physiological processes such as plant growth, development and immunity, including the suppression of biotic and abiotic stresses. In this paper, we report the synthesis of new brassinosteroid analogues with a nitrogen-containing side chain and their biological activity on Arabidopis thaliana. Based on molecular docking experiments, two groups of brassinosteroid analogues were prepared with short and long side chains in order to study the impact of side chain length on plants. The derivatives with a short side chain were prepared with amide, amine and ammonium functional groups. The derivatives with a long side chain were synthesized using amide and ammonium functional groups. A total of 25 new brassinosteroid analogues were prepared. All 25 compounds were tested in an Arabidopsis root sensitivity bioassay and cytotoxicity screening. The synthesized substances showed no significant inhibitory activity compared to natural 24-epibrassinolide. In contrast, in low concentration, several compounds (8a, 8b, 8e, 16e, 22a and 22e) showed interesting growth-promoting activity. The cytotoxicity assay showed no toxicity of the prepared compounds on cancer and normal cell lines.

scholarly journals Relationship of 25-hydroxyvitamin D3 side chain structure to biological activity.

1975 ◽  
Vol 250 (1) ◽  
pp. 226-230
Author(s):  
M F Holick ◽  
M Garabedian ◽  
H K Schnoes ◽  
H F DeLuca
Keyword(s):  
Biological Activity ◽  
Chain Structure ◽  
Side Chain ◽  
Relationship Of

Replacement of the interchain disulfide bridge-forming amino acids A7 and B7 by glutamate impairs the structure and activity of insulin

2004 ◽  
Vol 385 (12) ◽  
pp. 1171-1175 ◽  
Author(s):  
Zhan-Yun Guo ◽  
Xiao-Yuan Jia ◽  
You-Min Feng
Keyword(s):  
Biological Activity ◽  
Disulfide Bonds ◽  
Negative Charge ◽  
Disulfide Bridge ◽  
Site Directed Mutagenesis ◽  
Side Chain ◽  
Insulin Analogs ◽  
High Biological Activity ◽  
Chemical Groups ◽  
Structure And Activity

Abstract Insulin contains three disulfide bonds, one intrachain bond, A6–A11, and two interchain bonds, A7–B7 and A20–B19. Site-directed mutagenesis results (the two cysteine residues of disulfide A7–B7 were replaced by serine) showed that disulfide A7–B7 is crucial to both the structure and activity of insulin. However, chemical modification results showed that the insulin analogs still retained relatively high biological activity when A7Cys and B7Cys were modified by chemical groups with a negative charge. Did the negative charge of the modification groups restore the loss of activity and/or the disturbance of structure of these insulin analogs caused by deletion of disulfide A7–B7? To answer this question, an insulin analog with both A7Cys and B7Cys replaced by Glu, which has a long side-chain and a negative charge, was prepared by protein engineering, and its structure and activity were analyzed. Both the structure and activity of the present analog are very similar to that of the mutant with disulfide A7–B7 replaced by Ser, but significantly different from that of wild-type insulin. The present results suggest that removal of disulfide A7–B7 will result in serious loss of biological activity and the native conformation of insulin, even if the disulfide is replaced by residues with a negative charge.

scholarly journals Arsenoplatin-Ferritin Nanocage: Structure and Cytotoxicity

2021 ◽  
Vol 22 (4) ◽  
pp. 1874
Author(s):  
Giarita Ferraro ◽  
Alessandro Pratesi ◽  
Damiano Cirri ◽  
Paola Imbimbo ◽  
Daria Maria Monti ◽  
...  
Keyword(s):  
Biological Activity ◽  
Diffraction Data ◽  
Inductively Coupled Plasma ◽  
Emission Spectroscopy ◽  
Atomic Emission ◽  
Side Chain ◽  
Plasma Atomic Emission ◽  
Average Amount ◽  
X Ray ◽  
Inductively Coupled

Arsenoplatin-1 (AP-1), the prototype of a novel class of metallodrugs containing a PtAs(OH)2 core, was encapsulated within the apoferritin (AFt) nanocage. UV-Vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy measurements confirmed metallodrug encapsulation and allowed us to determine the average amount of AP-1 trapped inside the cage. The X-ray structure of AP-1-encapsulated AFt was solved at 1.50 Å. Diffraction data revealed that an AP-1 fragment coordinates the side chain of a His residue. The biological activity of AP-1-loaded AFt was comparatively tested on a few representative cancer and non-cancer cell lines. Even though the presence of the cage reduces the overall cytotoxicity of AP-1, it improves its selectivity towards cancer cells.

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