- Hydrogen bond surrogate stabilized water soluble 310-helix from a disordered pentapeptide containing coded α-amino acids
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Replacing a hypothetical i + 3 → i peptide H-bond in a disordered pentapeptide, that lacks any helicogenic Cα-tetrasubstituted residues, with a propyl linker and carbamylating the N-terminal nitrogen constrains it in the elusive 310-helical structure with high helicity and stability under varying conditions of temperature and pH, confirmed by NMR and CD analyses.
- Pal, Sunit,Prabhakaran, Erode N.
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supporting information
p. 2515 - 2519
(2018/05/28)
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- Continuous flow synthesis of β-amino acids from α-amino acids via Arndt-Eistert homologation
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A fully continuous four step process for the preparation of β-amino acids from their corresponding α-amino acids utilizing the Arndt-Eistert homologation approach is described. the Partner Organisations 2014.
- Pinho, Vagner D.,Gutmann, Bernhard,Kappe, C. Oliver
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p. 37419 - 37422
(2014/12/09)
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- CuI-promoted one-pot synthesis of N-boc protected β-ketotriazole amino acids: Application in the synthesis of new class of dipeptidomimetics
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One-pot click chemistry of Nα-Boc-bromomethylketones, NaN3 and propiolic acid affords N-Boc protected 1,4- disubstituted 1,2,3-β-ketotriazole acids in good to excellent yield. The use of CuI as catalyst and DMSO as solvent leads the click react
- Vishwanathaa,Narendra,Sureshbabu, Vommina V.
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experimental part
p. 308 - 314
(2012/07/17)
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- Design, synthesis and biological evaluation of a library of thiocarbazates and their activity as cysteine protease inhibitors
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Recently, we identified a novel class of potent cathepsin L inhibitors, characterized by a thiocarbazate warhead. Given the potential of these compounds to inhibit other cysteine proteases, we designed and synthesized a library of thiocarbazates containing diversity elements at three positions. Biological characterization of this library for activity against a panel of proteases indicated a significant preference for members of the papain family of cysteine proteases over serine, metallo-, and certain classes of cysteine proteases, such as caspases. Several potent inhibitors of cathepsin L and S were identified. The SAR data were employed in docking studies in an effort to understand the structural elements required for cathepsin S inhibition. This study provides the basis for the design of highly potent and selective inhibitors of the papain family of cysteine proteases.
- Liu, Zhuqing,Myers, Michael C.,Shah, Parag P.,Beavers, Mary Pat,Benedetti, Phillip A.,Diamond, Scott L.,Smith, Amos B.,Huryn, Donna M.
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experimental part
p. 337 - 351
(2010/09/04)
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- Potent and fully noncompetitive peptidomimetic inhibitor of multidrug resistance P-glycoprotein
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Nα-Boc-l-Asp(OBn)-l-Lys(Z)-OtBu (reversin 121, 1), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-l-proline (4(R)Hyp) gave compounds 11 and 15 characterized by half-maximal inhibitory concentrations (IC50) of 0.6 and 0.2 μM, which are 2-and 7-fold lower than that of the parent molecule. The difference in IC50 between 11 and 15 rests on the carbonyl group of the peptidyl bond, reduced in 15. Those compounds are rather specific of P-gp, having no or limited activity on MRP1 and BCRP. 15 displayed no marked cytotoxicity up to 10-fold its IC50. Importantly, 15 equally inhibited the Hoechst 33342 and daunorubicin effluxes through a typical noncompetitive inhibition mechanism, suggesting its binding to a site different from the H and R drug-transport sites.
- Arnaud, Ophélie,Koubeissi, Ali,Ettouati, Laurent,Terreux, Rapha?l,Alamé, Ghina,Grenot, Catherine,Dumontet, Charles,Di Pietro, Attilio,Paris, Jo?lle,Falson, Pierre
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supporting information; experimental part
p. 6720 - 6729
(2010/11/16)
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- Pentafluorophenyl-(tert-butoxycarbonylamino) methylcarbamates: Synthesis, isolation and application to the synthesis of ureidopeptides
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The one-pot synthesis of pentafluorophenyl-(tert-butoxycarbonylamino)methyl carbamates starting from N-Boc amino acids is described. Ultrasound mediated concomitant rearrangement and coupling reactions have resulted in the production of good yields of the active methyl carbamates. The carbamates have been employed as monomeric building blocks for the synthesis of dipeptidyl urea esters/acids. All the compounds obtained have been fully characterized by IR, 1H NMR, 13C NMR and mass spectroscopy.
- Sureshbabu, Vommina Venkata,Narendra,Kantharaju
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p. 920 - 926
(2008/12/23)
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- Synthesis and neuroprotective activity of analogues of glycyl-L-prolyl-L- glutamic acid (GPE) modified at the α-carboxylic acid
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The synthesis of nine GPE* analogues, wherein the α-carboxylic acid group of glutamic acid has been modified, is described by coupling readily accessible N-benzyloxycarbonyl-glycyl-l-proline 2 with various analogues of glutamic acid. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glutamate residue on the observed neuroprotective properties of the endogenous tripeptide GPE.
- Trotter, Nicholas S.,Brimble, Margaret A.,Harris, Paul W.R.,Callis, David J.,Sieg, Frank
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p. 501 - 517
(2007/10/03)
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- Linear and cyclic β3-oligopeptides with functionalised side-chains (-CH2OBn, -CO2Bn, -CH2CH2CO2Bn) derived from serine and from aspartic and glutamic acid
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The natural β-amino acid derivative Boc-Asp(β-OH)-OBn, as well as Boc-β-HGlu(OBn)-OH and Boc-β-HSer(OBn)-OH (prepared from appropriately protected glutamic acid and serine, respectively, by Arndt-Eistert homologation), were employed as building blocks for the synthesis of linear (11-20) and cyclic (21-23) β-oligopeptides consisting of two to six β-amino acids [using trichloroethyl (TCE) ester groups for C-terminal protection and pentafluorophenyl-ester activation for macrocyclisation]. While the linear derivatives are soluble enough for reactions and structural investigations in solution, the cyclo-β-tri- and -hexapeptides are not (according to FT-IR measurements they form networks of hydrogen bonds, perhaps consisting of so-called nanotubes). The CD spectra of the Boc-OTCE-protected (19) and of the unprotected (20) β-hexapeptides [β-Asp(OBn)-β-HGlu(OBn)-β-HSer(OBn)]2 differ drastically, and only the unprotected form shows the familiar pattern of a negative Cotton effect between 210 and 220 nm (indicative of a 314 helix). An NMR analysis in methanol of the β-hexapeptide 20 with free termini reveals the presence of a single, central, left-handed helix turn (14-membered hydrogen-bonded ring). The results are discussed and compared with those obtained previously for analogous β-peptides carrying non-functionalised side chains.
- Matthews, Jennifer L.,Gademann, Karl,Jaun, Bernhard,Seebach, Dieter
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p. 3331 - 3340
(2007/10/03)
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- Studies on selection blockers. 5. Design, synthesis, and biological profile of sialyl Lewis x mimetics based on modified serine-glutamic acid dipeptides.
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We have rationally designed a sLe(x) mimetic based on molecular modeling, synthesized type II and type II' beta-turn dipeptides (3a,b), and evaluated their biological profiles both in vitro and in vivo. Against E-selectin-sLe(x) binding, the type II beta-turn dipeptide L-Ser-D-Glu 3a (IC50, 13 microM) and the type II' beta-turn dipeptide D-Ser-L-Glu 3b (IC50, 5.5 microM) were 20-100-fold more potent blockers than sLe(x) (1; IC50, 600 microM) and a 3'-sulfated Le(x) analog (2; IC50, 280 microM). On the other hand, other stereoisomers, such as L-Ser-L-Glu 3c and D-Ser-D-Glu 3d, were very weak blockers, with IC50 > 1000 microM for both 3c,d. Against the P- and L-selectins, despite much different stereochemistry of compounds 3a-d, the dipeptides 3a-d were all more potent blockers than either sLe(x) or compound 2. Interestingly, compound 3b provided significant in vivo efficacy against an immunoglobulin E-mediated skin reaction in a mouse model. These findings indicate that sLe(x) mimetics with type II and type II' beta-turn dipeptides could be useful in the design of an active selectin blocker in vitro and/or in vivo.
- Tsukida,Hiramatsu,Tsujishita,Kiyoi,Yoshida,Kurokawa,Moriyama,Ohmoto,Wada,Saito,Kondo
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p. 3534 - 3541
(2007/10/03)
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- SYNTHESIS OF TRYPTAMINE DERIVATIVES OF L-5-HYDROXYTRYPTOPHAN
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In the search for new derivatives of 5-hydroxytryptophan that may be of value for pharmacological application, by methods of classical peptide synthesis we prepared 5-hydroxytryptophyl derivatives linked to a biogenic amine 2-(5-methoxy-3-indolyl)ethylami
- Ivanova, E. V.,Popova, G. V.,Suvorov, N. N.
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p. 385 - 390
(2007/10/02)
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- SYNTHESIS AND IMMUNOREGULATORY PROPERTIES OF FRAGMENTS OF A PROLINE-RICH POLYPEPTIDE FROM OVINE COLOSTRUM
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Proline-rich-polypeptide (PRP) isolated from ovine colostrum produces a regulatory effect on the immune response.A nonapeptide fragment of PRP obtained by chymotryptic digestion (Val-Glu-Ser-Tyr-Val-Pro-Leu-Phe-Pro) shows biological activity similar to PR
- Kubik, Aleksandra,Szewczuk, Zbigniew,Siemion, Ignacy Z.,Janusz, Maria,Wieczorek, Zbigniew,et al.
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p. 457 - 464
(2007/10/02)
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