- Active Controlled and Tunable Coacervation Using Side-Chain Functional α-Helical Homopolypeptides
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We report the development of new side-chain amino acid-functionalized α-helical homopolypeptides that reversibly form coacervate phases in aqueous media. The designed multifunctional nature of the side-chains was found to provide a means to actively control coacervation via mild, biomimetic redox chemistry as well as allow response to physiologically relevant environmental changes in pH, temperature, and counterions. These homopolypeptides were found to possess properties that mimic many of those observed in natural coacervate forming intrinsically disordered proteins. Despite ordered α-helical conformations that are thought to disfavor coacervation, molecular dynamics simulations of a polypeptide model revealed a high degree of side-chain conformational disorder and hydration around the ordered backbone, which may explain the ability of these polypeptides to form coacervates. Overall, the modular design, uniform nature, and ordered chain conformations of these polypeptides were found to provide a well-defined platform for deconvolution of molecular elements that influence biopolymer coacervation and tuning of coacervate properties for downstream applications.
- Barun, Ehab,Bell, Alexandra G.,Deming, Timothy J.,Evans, Declan,Gharakhanian, Eric G.,Houk, K. N.,Scott, Wendell A.
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supporting information
p. 18196 - 18203
(2021/11/12)
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- Evidence and exploitation of dicationic ammonium-nitrilium superelectrophiles: direct synthesis of unsaturated piperidinones
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Exploiting superacid activation, the reactivity of aminonitriles was enhanced through the transient formation of highly reactive ammonium-nitrilium superelectrophiles. Demonstrated by usingin situlow-temperature NMR experiments and confirmed by X-ray diffraction analysis, these dications can be intramolecularly trapped by non-activated alkenes to generate unsaturated piperidinones, including enantioenriched ones, in a straightforward way.
- Cantin, Thomas,Morgenstern, Yvonne,Mingot, Agnès,Kornath, Andreas,Thibaudeau, Sébastien
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supporting information
p. 11110 - 11113
(2020/10/05)
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- The: Ortho -substituent on 2,4-bis(trifluoromethyl)phenylboronic acid catalyzed dehydrative condensation between carboxylic acids and amines
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2,4-Bis(trifluoromethyl)phenylboronic acid is a highly effective catalyst for dehydrative amidation between carboxylic acids and amines. Mechanistic studies suggest that a 2:2 mixed anhydride is expected to be the only active species, and the ortho-substituent of boronic acid plays a key role in preventing the coordination of amines to the boron atom of the active species, thus accelerating the amidation. This catalyst works for α-dipeptide synthesis.
- Wang, Ke,Lu, Yanhui,Ishihara, Kazuaki
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supporting information
p. 5410 - 5413
(2018/05/30)
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- Synthesis of chiral TFA-protected α-amino aryl-ketone derivatives with friedel-crafts acylation of α-amino acid n-hydroxysuccinimide ester
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Chiral N-protected α-amino aryl-ketones are one of the useful precursors used in the synthesis of various biologically active compounds and can be constructed via Friedel-Crafts acylation of N-protected α-amino acids. One of the drawbacks of this reaction
- Tachrim, Zetryana Puteri,Oida, Kazuhiro,Ikemoto, Haruka,Ohashi, Fumina,Kurokawa, Natsumi,Hayashi, Kento,Shikanai, Mami,Sakihama, Yasuko,Hashidoko, Yasuyuki,Hashimoto, Makoto
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supporting information
(2017/11/07)
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- Direct, visible light-sensitized benzylic C[sbnd]H fluorination of peptides using dibenzosuberenone: selectivity for phenylalanine-like residues
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A visible light-sensitized benzylic sp3C[sbnd]H fluorination protocol using dibenzosuberenone (5?mol?%) and Selectfluoris optimized for the direct functionalization of phenylalanine-like residues in short chain peptides. Amino acids, dipeptides, and tripeptides undergo benzylic fluorination with remarkable regioselectivity in the presence of protected basic, acidic, and nonpolar side chains (including those with tertiary sites). Additionally, protecting group compatibility, a gram scale application, and competition experiments were explored.
- Bume, Desta Doro,Pitts, Cody Ross,Jokhai, Rayyan Trebonias,Lectka, Thomas
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supporting information
p. 6031 - 6036
(2016/09/16)
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- Human and rat monoamine oxidase-A are differentially inhibited by (S)-4-alkylthioamphetamine derivatives: Insights from molecular modeling studies
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Four enantiomerically pure (S)-4-alkylthioamphetamine derivatives were evaluated as monoamine oxidase (MAO) inhibitors using the human and rat isoforms of the enzyme. Molecular dockings were performed in order to gain insights regarding the binding mode o
- Fierro, Angelica,Osorio-Olivares, Mauricio,Cassels, Bruce K.,Edmondson, Dale E.,Sepulveda-Boza, Silvia,Reyes-Parada, Miguel
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p. 5198 - 5206
(2008/03/15)
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- A two-step method for the preparation of homochiral cathinones
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A simple method for the preparation of homochiral ring-substituted 1-aryl-2-aminopropanones 2 ('cathinones') is described, involving initial Friedel-Crafts acylation of aromatics with (S)- or (R)-N-trifluoroacetylalanyl chloride, followed by acid hydrolysis of the intermediate trifluoroacetamido intermediates 1, for which X-ray diffraction analysis confirmed the structures.
- Osorio-Olivares, Mauricio,Rezende, Marcos Caroli,Sepulveda-Boza, Silvia,Cassels, Bruce K.,Baggio, Ricardo F.,Munoz-Acevedo, Juan C.
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p. 1473 - 1477
(2007/10/03)
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- Enantiospecific synthesis and pharmacological evaluation of a series of super-potent, conformationally restricted 5-HT2A/2C receptor agonists
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The affinity of ligands for either the 5-HT2A or 5-HT2C agonist binding site was enhanced by modification of the 2,5-oxygen substituents that are found in typical hallucinogenic amphetamines such as 4b (DOB). Restriction of the conformationally flexible 2,5-dimethoxy substituents into fused dihydrofuran rings generally resulted in increased potency relative to the parent 2,5-dimethoxy compounds. The pure enantiomers of these arylalkylamines were obtained by enantiospecific synthesis that involved acylation of the heterocyclic nucleus 7 with N-trifluoroacetyl-protected D- or L-alanyl chloride, followed by ketone reduction and N-deprotection. The enantiomers demonstrated modest stereoselectivity at the two receptors. Several general trends within these classes of new compounds were observed during their pharmacological investigation. For most pairs of optical isomers tested, the R-enantiomers of the compounds containing heterocycle 7 bound with only slightly higher affinity than their S-antipodes at the 5-HT2A and 5-HT2C receptors. Likewise, functional studies indicated that the R-enantiomers generally displayed increased potency compared to the S-enantiomers. Aromatization of the dihydrofuran rings of these arylalkylamines further increased affinity and potency. Only a few compounds were full agonists with most of them possessing intrinsic activities in the range of 60-80%. These compounds with a fully aromatic linear tricyclic nucleus are some of the highest-affinity ligands for the 5-HT2A receptor reported to date.
- Chambers,Kurrasch-Orbaugh,Parker,Nichols
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p. 1003 - 1010
(2007/10/03)
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- Regioselective functionalization of chiral nickelacycles derived from N-protected aspartic and glutamic anhydrides
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The electrophilic cleavage of the nickelacycles resulting from oxidative addition of Ni(o) complexes to N-protected aspartic and glutamic anhydrides, followed by decarbonylation, gives rise regioselectively to derivatives of α- and β-alanine or α- and γ-aminobutyric acid, respectively.
- Castano,Echavarren
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p. 4783 - 4786
(2007/10/02)
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- ENANTIOSELECTIVE SYNTHESES OF α-AMINO ACIDS FROM 10-SULFONAMIDO-ISOBORNYL ESTERS AND DI-t-BUTYL AZODICARBOXYLATE
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Successive treatment of chiral esters 7 with LDA/Me3SiCl and di-t-butyl azodicarboxylate/TiCl4 and Ti(OiPr)4 gave N,N-di-t-butoxycarbonylhydrazinoesters 11 which on deacylation, hydrogenolysis, transesterification and acidic hydrolysis furnished (2S)-α-amino acid hydrochlorides 13 in good overall yields, high enantiomeric purity and with efficient recovery of the alcohol auxiliary 4.Experimental evidence for the configuration and conformation of the intermediate O-silyl ketene acetals 1 is provided.
- Oppolzer, Wolfgang,Moretti, Robert
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p. 5541 - 5552
(2007/10/02)
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- Effect of N-trifluoroacetyl derivatives of amino acids and amino acid analogs on microbial antitumor screen
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Eighteen trifluoroacetyl derivatives of amino acids and of amino acid analogs were prepared and tested for growth-inhibitory activity. Of the compounds tested, the trifluoroacetyl derivatives of o-, m-, and p-fluorophenylalanine and β-3-thienylalanine showed modest activity; trifluoroacetyl derivatives of phenylalanine and of β-2-thienylalanine showed marginal activity. The activity exhibited by the active trifluoroacetyl compounds was equal to that noted for most active chloroacetyl derivatives reported previously, as judged by comparison of their activity with that of chloroacetyl-m-fluorophenylalanine. No reversal of inhibition was noted when a representative of these inhibitors was challenged with a corresponding natural metabolite, both as free amino acid and as a noninhibitory acylated compound.
- Otani,Briley
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p. 496 - 499
(2007/10/05)
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