Design and synthesis of amidine-type peptide bond isosteres: application of nitrile oxide derivatives as active ester equivalents in peptide and peptidomimetics synthesis

Eriko Inokuchi; Ai Yamada; Kentaro Hozumi; Kenji Tomita; Shinya Oishi; Hiroaki Ohno; Motoyoshi Nomizu; Nobutaka Fujii

doi:10.1039/c0ob01193b

Design and Synthesis of a Cyclic Double-Grafted Polymer Using Active Ester Chemistry and Click Chemistry via A “Grafting onto” Method

Polymers ◽

10.3390/polym11020240 ◽

2019 ◽

Vol 11 (2) ◽

pp. 240 ◽

Cited By ~ 1

Author(s):

Meng Liu ◽

Lu Yin ◽

Shuangshuang Zhang ◽

Zhengbiao Zhang ◽

Wei Zhang ◽

...

Keyword(s):

Molecular Weight ◽

Click Chemistry ◽

Narrow Molecular Weight Distribution ◽

Grafted Polymers ◽

Azide Group ◽

Double Chain ◽

Grafted Polymer ◽

Design And Synthesis ◽

Active Ester ◽

Grafting Onto

Combing active ester chemistry and click chemistry, a cyclic double-grafted polymer was successfully demonstrated via a “grafting onto” method. Using active ester chemistry as post-functionalized modification approach, cyclic backbone (c-P2) was synthesized by reacting propargyl amine with cyclic precursor (poly(pentafluorophenyl 4-vinylbenzoate), c-PPF4VB6.5k). Hydroxyl-containing polymer double-chain (l-PS-PhOH) was prepared by reacting azide-functionalized polystyrene (l-PSN3) with 3,5-bis(propynyloxy)phenyl methanol, and further modified by azide group to generate azide-containing polymer double-chain (l-PS-PhN3). The cyclic backbone (c-P2) was then coupled with azide-containing polymer double-chain (l-PS-PhN3) via CuAAC reaction to construct a novel cyclic double-grafted polymer (c-P2-g-Ph-PS). This research realized diversity and complexity of side chains on cyclic-grafted polymers, and this cyclic double-grafted polymer (c-P2-g-Ph-PS) still exhibited narrow molecular weight distribution (Mw/Mn < 1.10).

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Short Peptides with Uncleavable Peptide Bond Mimetics as Photoactivatable Caspase-3 Inhibitors

Molecules ◽

10.3390/molecules24010206 ◽

2019 ◽

Vol 24 (1) ◽

pp. 206

Author(s):

Tim Van Kersavond ◽

Raphael Konopatzki ◽

Suravi Chakrabarty ◽

Bernhard Blank-Landeshammer ◽

Albert Sickmann ◽

...

Keyword(s):

Caspase 3 ◽

Solid Phase ◽

Solid Phase Peptide Synthesis ◽

Covalent Bond ◽

Peptide Bond ◽

Covalent Modification ◽

Chemical Probes ◽

Design And Synthesis ◽

Peptide Aldehydes ◽

Protease Substrate

Chemical probes that covalently interact with proteases have found increasing use for the study of protease function and localization. The design and synthesis of such probes is still a bottleneck, as the strategies to target different families are highly diverse. We set out to design and synthesize chemical probes based on protease substrate specificity with inclusion of an uncleavable peptide bond mimic and a photocrosslinker for covalent modification of the protease target. With caspase-3 as a model target protease, we designed reduced amide and triazolo peptides as substrate mimetics, whose sequences can be conveniently constructed by modified solid phase peptide synthesis. We found that these probes inhibited the caspase-3 activity, but did not form a covalent bond. It turned out that the reduced amide mimics, upon irradiation with a benzophenone as photosensitizer, are oxidized and form low concentrations of peptide aldehydes, which then act as inhibitors of caspase-3. This type of photoactivation may be utilized in future photopharmacology experiments to form protease inhibitors at a precise time and location.

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Design and Synthesis of (3,5-Disubstituted Isoxazole)-Linked [1,5]-Benzodiazepine Conjugates: Evaluation of their Antimicrobial and Anti-Tyrosinase Activities

Journal of Chemical Research ◽

10.3184/174751917x14815427219121 ◽

2017 ◽

Vol 41 (1) ◽

pp. 12-17 ◽

Cited By ~ 1

Author(s):

Wejdane Abdallah ◽

Mejda Daami-Remadi ◽

Mansour Znati ◽

Hichem Ben Jannet ◽

Rafik Gharbi

Keyword(s):

2D Nmr ◽

Nitrile Oxide ◽

Design And Synthesis ◽

Hybrid Molecules ◽

Nmr Techniques ◽

Benzodiazepine Derivatives

A series of novel 2-(3,5-disubstituted isoxazolyl)-1,5-benzodiazepines and 2,4-bis-(3,5-disubstituted isoxazolyl)-1,5-benzodiazepine derivatives have been designed and synthesised by employing an alkyne/nitrile oxide cycloaddition ‘click’ type chemistry protocol. The structures of the compounds were determined on the basis of 1H, 13C and 2D-NMR techniques and by HRMS analysis. These hybrid molecules exhibit moderate to significant antimicrobial and anti-tyrosinase activities.

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Facile Peptide-Bond Formation Using Polystyrene-Bound o-Nitrophenol as an Active Ester

Journal of the Chinese Chemical Society ◽

10.1002/jccs.199300075 ◽

1993 ◽

Vol 40 (5) ◽

pp. 475-479

Author(s):

Shui-Chyr Duh ◽

Hsiao-Zeng Hsieh ◽

Shui-Tein Chen ◽

Kung-Tsung Wang

Keyword(s):

Bond Formation ◽

Peptide Bond ◽

Peptide Bond Formation ◽

Active Ester

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Design and synthesis of a hydrogen peroxide-responsive amino acid that induces peptide bond cleavage after exposure to hydrogen peroxide

Tetrahedron Letters ◽

10.1016/j.tetlet.2015.05.060 ◽

2015 ◽

Vol 56 (28) ◽

pp. 4228-4231 ◽

Cited By ~ 5

Author(s):

Miku Kita ◽

Jun Yamamoto ◽

Takuya Morisaki ◽

Chiaki Komiya ◽

Tsubasa Inokuma ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Amino Acid ◽

Bond Cleavage ◽

Peptide Bond ◽

Peptide Bond Cleavage ◽

Design And Synthesis

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Prostatic Acid Phosphatase (PAP) Differentiated Ultracytochemically from Lysosomal Acid Phosphate in the Rat with a PAP/Specific Substrate, Phosphorylcholine

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100115870 ◽

1975 ◽

Vol 33 ◽

pp. 450-451

Author(s):

W. Allen Shannon ◽

José A. Serrano ◽

Hannah L. Wasserkrug ◽

Anna A. Serrano ◽

Arnold M. Seligman

Keyword(s):

Acid Phosphatase ◽

Phosphate Buffer ◽

Prostatic Carcinoma ◽

Prostatic Acid Phosphatase ◽

Chemotherapeutic Agents ◽

Specific Substrate ◽

Acid Phosphate ◽

Lysosomal Acid ◽

Design And Synthesis ◽

New Chemotherapeutic Agents

During the design and synthesis of new chemotherapeutic agents for prostatic carcinoma based on phosphorylated agents which might be enzyme-activated to cytotoxicity, phosphorylcholine, [(CH3)3+NCH2CH2OPO3Ca]Cl-, has been indicated to be a very specific substrate for prostatic acid phosphatase (PAP). This phenomenon has led to the development of specific histochemical and ultracytochemical methods for PAP using modifications of the Gomori lead method for acid phosphatase. Comparative histochemical results in prostate and kidney of the rat have been published earlier with phosphorylcholine (PC) and β-glycerophosphate (βGP). We now report the ultracytochemical results.Minced tissues were fixed in 3% glutaraldehyde-0.1 M phosphate buffered (pH 7.4) for 1.5 hr and rinsed overnight in several changes of 0.05 M phosphate buffer (pH 7.0) containing 7.5% sucrose. Tissues were incubated 30 min to 2 hr in Gomori acid phosphatase medium (2) containing 0.1 M substrate, either PC or βGP.

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Tailoring microstructures of materials through biomimetics

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100148332 ◽

1993 ◽

Vol 51 ◽

pp. 500-501

Author(s):

Mehmet Sarikaya ◽

Ilhan A. Aksay

Keyword(s):

Chemical Properties ◽

Design And Synthesis ◽

Structure Sensitive ◽

Macro Scale ◽

Methods Of Synthesis ◽

Successive Level ◽

Engineering Materials ◽

Physical And Chemical ◽

And Chemical Properties ◽

Synthesis Of Materials

Biomimetics involves investigation of structure, function, and methods of synthesis of biological composite materials. The goal is to apply this information to the design and synthesis of materials for engineering applications.Properties of engineering materials are structure sensitive through the whole spectrum of dimensions from nanometer to macro scale. The goal in designing and processing of technological materials, therefore, is to control microstructural evolution at each of these dimensions so as to achieve predictable physical and chemical properties. Control at each successive level of dimension, however, is a major challenge as is the retention of integrity between successive levels. Engineering materials are rarely fabricated to achieve more than a few of the desired properties and the synthesis techniques usually involve high temperature or low pressure conditions that are energy inefficient and environmentally damaging.In contrast to human-made materials, organisms synthesize composites whose intricate structures are more controlled at each scale and hierarchical order.

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Role of the Small (40S) Subunits in the Structure of the Interface of Eukaryotic Ribosomes

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002427 ◽

1980 ◽

Vol 38 ◽

pp. 548-549

Author(s):

M. Boublik ◽

N. Robakis ◽

W. Hellmann ◽

F. Jenkins

Keyword(s):

Structural Similarity ◽

High Resolution Electron Microscopy ◽

Peptide Bond ◽

Uranyl Acetate ◽

Mutual Orientation ◽

Mutual Position ◽

Peptide Bond Formation ◽

Resolution Electron ◽

Direct Technique ◽

Structural Details

Ribosomes are ribonucleoprotein particles which process the genetic information coded in mRNA into protein synthesis. The analogy in function and composition of ribosomes from various sources, both prokaryotic and eukaryo-tic, imply a structural similarity. At present, high resolution electron microscopy is the most direct technique with a potential to resolve the extent of the structural homology of ribosomal particles at a macromolecular level. The structure of ribosomes is highly complex as a result of the large number of their constituents. In general, 80S eukaryotic monosomes consist of two uneven subunits - large (60S) and small (40S) - accomodating four different RNAs and approximately 80 different proteins. Mutual orientation of both subunits on the monosome is of particular interest because it determines the interface, the supposed site of interactions of ribosomes with other macro-molecules involved in peptide bond formation. Since entrapping of the contrasting solution (0.5% aqueous uranyl acetate) obscures all structural details in the interface, information on its architecture is limited to an indirect reconstruction based on the established 3-D structure of both sub-units and their mutual position after association.

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