- A synthetic ditryptophan conjugate that rescues bacteria from mercury toxicity through complexation
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The synthesis of ditryptophan-pyridine conjugates and their binding to mercury ions is described. Conjugate 3 shows an excellent ability to sequester mercury from solution and rescue bacterial growth in a concentration-dependent survival assay. It is proposed that such compounds, composed primarily of bioessential/biodegradable components, could be potentially used as sequestrating agents for the removal of Hg(II) ions in detoxification strategies.
- Mondal, Sudipta,Swaroop, Shiv,Gurunath, Ramanathan,Verma, Sandeep
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- Second harmonic optical activity of tryptophan derivatives adsorbed at the air/water interface
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Optical activity in second harmonic reflection from the air/water interface of solutions of simple tryptophan (trp) derivatives has been investigated. The derivatives include D- and L-optical isomers of Boc-trp and DD- and LL-isomers of the dipeptide Boc-trp-trp, where Boc is tert-butyloxycarbonyl. An experimental method based on polarization modulation of fundamental radiation by rotation of a quarter-wave retardation plate has been used to completely characterize the second-order nonlinear susceptibilities of the chiral surfaces, for the fundamental wavelength ?? = 564 nm. Boc-trp and Boc-trp-trp show similar chiral contributions to the nonlinear susceptibilities, which indicates that the chiral response does not depend on intramolecular interactions between trp residues. The efficiency of second harmonic reflection has been shown to be resonantly enhanced at the two-photon level, in the region of the near-UV bands (a??280 nm) of the indole chromophore of tryptophan. The origin of the chiral response is discussed in terms of simple microscopic models, and a comparison is made with optical activity of tryptophanyl compounds in linear spectroscopy. The peptide gramicidin, incorporating several trp residues, showed no evidence of optical activity in second harmonic reflection from the air/water interface. This indicates that second harmonic optical activity is sensitive to structural effects such as conformational and orientational distributions of trp residues at the interface.
- Mitchell,McAloney
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- Biomimetic approaches to diazonamide A. Direct synthesis of the indole bis-oxazole fragment by oxidation of a TyrValTrpTrp tetrapeptide
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Oxidation of a protected TyrValTrpTrp tetrapeptide results in direct formation of the indole bis-oxazole core of diazonamide A. The Royal Society of Chemistry 2006.
- Sperry, Jonathan,Moody, Christopher J.
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- Photochemical Chemoselective Alkylation of Tryptophan-Containing Peptides
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We report a photochemical method for the chemoselective radical functionalization of tryptophan (Trp)-containing peptides. The method exploits the photoactivity of an electron donor-acceptor complex generated between the tryptophan unit and pyridinium sal
- Laroche, Benjamin,Tang, Xinjun,Archer, Gaétan,Di Sanza, Riccardo,Melchiorre, Paolo
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supporting information
p. 285 - 289
(2021/01/26)
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- A novel molecular scaffold resensitizes multidrug-resistant S. aureus to fluoroquinolones
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Nosocomial infections arising from opportunistic pathogens, such as Staphylococcus aureus, are growing unabated, compounded by the rapid emergence of antimicrobial resistance. Herein, we demonstrate a new molecular design that exhibits excellent activity against multidrug-resistant S. aureus with no cytotoxicity and resensitizes fluoroquinolones (FQ) towards FQ-resistant methicillin-resistant S. aureus strains, with DNA gyrase B as the likely molecular target as determined by molecular dynamics (MD) simulations.
- Panjla, Apurva,Kaul, Grace,Shukla, Manjulika,Tripathi, Shubhandra,Nair, Nisanth N.,Chopra, Sidharth,Verma, Sandeep
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supporting information
p. 8599 - 8602
(2019/07/25)
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- MITHRAMYCIN DERIVATIVES HAVING INCREASED SELECTIVITY AND ANTI-CANCER ACTIVITY
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Mithramycin side chain carboxylic acid (MTM-SA) derivative are provided, which include a substituted amino acid derivative, a substituted amino acid dipeptide derivative, or an unsubstituted dipeptide derivative. The MTM-SA derivatives are useful for treatment of cancer or neuro-diseases associated with an aberrant erythroblast transformation-specific transcription factor. Unique MTM-SA derivatives have increased selectively toward ETS transcription factor.
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Paragraph 0095; 0122
(2019/04/05)
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- Development of Mithramycin Analogues with Increased Selectivity toward ETS Transcription Factor Expressing Cancers
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Mithramycin A (1) was identified as the top potential inhibitor of the aberrant ETS transcription factor EWS-FLI1, which causes Ewing sarcoma. Unfortunately, 1 has a narrow therapeutic window, compelling us to seek less toxic and more selective analogues. Here, we used MTMSA (2) to generate analogues via peptide coupling and fragment-based drug development strategies. Cytotoxicity assays in ETS and non-ETS dependent cell lines identified two dipeptide analogues, 60 and 61, with 19.1- and 15.6-fold selectivity, respectively, compared to 1.5-fold for 1. Importantly, the cytotoxicity of 60 and 61 is 100 nM in ETS cells. Molecular assays demonstrated the inhibitory capacity of these analogues against EWS-FLI1 mediated transcription in Ewing sarcoma. Structural analysis shows that positioning the tryptophan residue in a distal position improves selectivity, presumably via interaction with the ETS transcription factor. Thus, these analogues may present new ways to target transcription factors for clinical use.
- Mitra, Prithiba,Eckenrode, Joseph M.,Mandal, Abhisek,Jha, Amit K.,Salem, Shaimaa M.,Leggas, Markos,Rohr, Jürgen
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p. 8001 - 8016
(2018/09/06)
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- Catalytic enantioselective acyl transfer: the case for 4-PPY with a C-3 carboxamide peptide auxiliary based on synthesis and modelling studies
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A series of 4-pyrrolidinopyridine (4-PPY) C-3 carboxamides containing peptide-based side chains have been synthesised and evaluated in the kinetic resolution of a small library of chiral benzylic secondary alcohols. A key design element was the incorporation of a tryptophan residue in the peptide side chain for promoting π-stacking between peptide side chain and the pyridinium ring of the N-acyl intermediate, in which modelling was used as a structure-based guiding tool. Together, a catalyst containing a LeuTrp-N-Boc side chain (catalyst 8) was identified that achieved s-values up to and in slight excess of 10. A transition-state model based on the modelling is proposed to explain the origin of enantioselectivity. This study establishes the usefulness of modelling as a structure-based guiding tool for enantioselectivity optimization as well as the potential for developing scalable peptide-based DMAP-type catalysts for large-scale resolution work.
- Cozett, Rudy E.,Venter, Gerhard A.,Gokada, Maheswara Rao,Hunter, Roger
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supporting information
p. 10914 - 10925
(2016/12/06)
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- Modular incorporation of 1-benzyltryptophan into dipeptide hosts that bind acetylcholine in pure water
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Proteins that recognize and bind quaternary ammonium ions depend on " aromatic-cage " structural motifs that use multiple aromatic residues to engage the side chain's ammonium cation. We introduce herein the use of 1-benzyltryp- tophan (Trp(Bn)) residues as synthetic, unnatural partial analogues of natural aromatic cages. We demonstrate the modular incorporation of these building blocks into simple dipeptide hosts and show that they are capable of binding quaternary ammonium ions in buffered water and in chloroform.
- Beshara, Cory S.,Hof, Fraser
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supporting information; experimental part
p. 1009 - 1016
(2011/02/16)
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- Diazonamide studies. A direct synthesis of the indole bis-oxazole fragment from tri- and tetra-peptides using biomimetic oxidative cyclizations
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The oxidation of several readily prepared tryptophan containing tri- and tetrapeptides with DDQ results in a biomimetic cyclization and direct formation of the indole bis-oxazole fragment of diazonamide A, establishing that such a transformation is a viab
- Sperry, Jonathan,Moody, Christopher J.
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experimental part
p. 6483 - 6495
(2010/10/19)
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- Sunlight mediated disruption of peptide-based soft structures decorated with gold nanoparticles
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This communication reports morphological studies of a novel C 3-symmetric thiolated, tren-based ditryptophan conjugate. The exposed thiol groups on the soft structures interacted with gold nanoparticles and mediated the release of encapsulated fluorescent dye, when exposed to natural sunlight.
- Barman, Apurba Kr.,Verma, Sandeep
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supporting information; experimental part
p. 6992 - 6994
(2010/10/19)
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- Synthesis, characterization and DNA binding and cleavage properties of copper(II)-tryptophan-tryptophan complex
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Reaction of copper(II) with tryptophan-tryptophan yields a 1:2 chloro bis(trp-trp) cuprate(II) complex. The complex exhibits absorption band at 620 nm (ε = 130 M-1 cm-1), which suggests a square pyramidal geometry at Cu(II) as observed for other Cu(II)-peptide complexes. The giso value of 2.09 for the complex agrees with a Cu(II) environment of distorted square pyramidal geometry. The mononuclear complex binds to calf thymus DNA through moderate intercalative and weak covalent interactions. It converts the supercoiled plasmid pUC19 DNA to the nicked circular form under physiological conditions.
- Reddy, Pulimamidi R.,Raju, Nomula,Reddy, Karnati V.
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experimental part
p. 1638 - 1643
(2010/06/18)
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- Participation of aromatic side chains in diketopiperazine ensembles
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This study probes the beneficial role of aromatic side chains in peptide self-assembly by choosing four diketopiperazine model systems variably composed of glycine, proline, phenylalanine, and tryptophan residues.
- Joshi,Verma, Sandeep
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p. 4231 - 4234
(2008/09/21)
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- Ditryptophan conjugation triggers conversion of biotin fibers into soft spherical structures
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(Figure Presented) Trigger happy: Biotin and its methyl ester form long fibers in solution, which are transformed into soft spherical structures upon simple conjugation with ditryptophan dipeptide (see picture). Such morphogenesis is not achieved in a controlled fashion by other aromatic amino acids.
- Joshi,Verma, Sandeep
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supporting information; experimental part
p. 2860 - 2863
(2009/02/06)
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- Interaction between quaternary ammonium ions and dipeptides: Positive anion allosteric effect
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The binding properties of dipeptides possessing aromatic residues towards quaternary ammonium ions have been investigated by 1H-NMR spectroscopy. The intermolecular hydrogen bonding between exchangeable protons (OH and NH) of aromatic residues
- Ito, Kazuaki,Nagase, Kayo,Morohashi, Naoya,Ohba, Yoshihiro
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- Selective inhibitors of the serine protease plasmin: Probing the S3 and S3′ subsites using a combinatorial library
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A combinatorial library of 400 serine protease inhibitors with the general structure Cbz-Xaa-Trp-cyclohexanone-Trp-Yaa-OH has been constructed. The library was synthesized on the solid phase using mix-and-split synthesis, where 20 di
- Xue, Fengtian,Seto, Christopher T.
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p. 6908 - 6917
(2007/10/03)
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- Novel tryptophan-derived dipeptides and bioactive metabolites from the sea hare Aplysia dactylomela
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Dactylamides A (1) and B (2), two new tryptophan-derived dipeptides were isolated from the sea hare Aplysia dactylomela and structurally characterised by spectroscopic methods and synthesis of deoxy-analogues. Isolaurenisol, allolaurinterol, their respective acetates and aplysioviolin, isolated as the bioactive constituents of the sea hare, were also structurally characterised and evaluated in a range of biological assays.
- Appleton, David R,Babcock, Russell C,Copp, Brent R
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p. 10181 - 10189
(2007/10/03)
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- The structure and conformation of the tryptophanyl diketopiperazines cyclo(Trp-Trp)·C2H6SO and cyclo(Trp-Pro)
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The structure and conformation of the cyclic dipeptides [cyclo(L-Trp-L-Trp)·C2H6SO] and cyclo(L-Trp-L-Pro) have been investigated with X-ray crystallographic and spectroscopic methods. Cyclo(L-tryptophanyl-L-tryptophanyl)·DMSO solvate crystallized in the space group P212121 with cell dimensions a = 6.193(2), b = 11.545(3), c = 31.117(4) A. The crystal structure is stabilized by four hydrogen bonds (three intermolecular hydrogen bonds and one intramolecular bond). The first intermolecular bond is between the oxygen of DMSO and the nitrogen of indole ring 2, in contrast to the second intramolecular hydrogen bond between the nitrogen of indole ring 1 and the oxygen of DMSO. The two remaining intermolecular hydrogen bonds are between the nitrogens of the DKP ring and the carbonyl oxygens of the DKP ring. The values of X1A1 (-45.764) and X1A2 (67.437) indicate an extended side chain conformation for Trp residue 1 (EN) and a folded conformation for Trp residue 2. The DKP ring is more planar than in other cyclic dipeptide compounds (φ1 = 11.414, ψ1 = -7.516, φ2 = 12.471, and ψ2 = -8.256). In cyclo(L-Trp-L-Trp) the Cβ resonance of L-tryptophan (29.88 ppm) is shifted upfield 0.82 ppm when compared with the same resonance in cyclo(L-Trp-L-Gly) (30.7 ppm) and cyclo(L-Leu-L-Trp) (30.7 ppm). Two conformations of cyclo(Trp-Pro) crystallized in the space group P1 with cell dimensions a = 5.422(1), b = 9.902(1), c = 13.443(2) A, α = 80.42(1), β = 78.61(1), and γ = 89.13(1)°. The conformation of the backbone and the orientation of the aromatic side chains for these conformers are very similar. The DKP rings for both conformers adopt a typical boat conformation in contrast to the flattened chair conformation observed for cyclo(Tyr-Pro) and cyclo(Phe-F-Pro). The tryptophan side chains of these conformers are folded towards the diketopiperazine (DKP) ring. The pyrrolidine ring for conformer 1 can be described as an envelope (Cs-Cβ-endo) conformation in contrast to the pyrrolidine ring symmetry for conformer 2 which is an intermediate between Cs and C2 rather than pure Cs for the proline ring with Cβ-endo and Cγ-exo with respect to C′. The two prolyl rings are puckered at the β-carbon atoms which deviate from the best planes defined by the four remaining atoms. The crystal structures are stabilized by four intermolecular hydrogens bonds. An intermolecular bond between the nitrogen of the indole ring (conformer 1) and the carbonyl oxygen of the DKP ring (conformer 2) was observed. The second hydrogen bond is between the nitrogen of the indole ring (conformer 2) and the carbonyl oxygen of the DKP ring (conformer 1). The last two hydrogens involve the carbonyl oxygens of the DKP rings and the nitrogens of the DKP rings [carbonyl oxygen of DKP ring (conformer 1) - nitrogen of DKP ring (conformer 2); nitrogen of DKP ring (conformer 1) - carbonyl oxygen of DKP ring (conformer 2)].
- Grant,Hunt,Milne,Roos,Joubert
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p. 435 - 447
(2007/10/03)
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- PENTAFLUOROPHENYL DIPHENYLPHOSPHINATE A NEW EFFICIENT COUPLING REAGENT IN PEPTIDE CHEMISTRY
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Pentafluorophenyl diphenylphosphinate was found to be a new efficient coupling reagent for the racemization-free synthesis of peptides.It has been applied in both the solution and the solid phase peptide synthesis.
- Chen, Shaoqing,Xu, Jiecheng
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p. 6711 - 6714
(2007/10/02)
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