- Influence of Sulfur-Containing Diamino Acid Structure on Covalently Crosslinked Copolypeptide Hydrogels
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Biologically occurring non-canonical di-α-amino acids were converted into new di-N-carboxyanhydride (di-NCA) monomers in reasonable yields with high purity. Five different di-NCAs were separately copolymerized with tert-butyl-l-glutamate NCA to obtain covalently crosslinked copolypeptides capable of forming hydrogels with varying crosslinker density. Comparison of hydrogel properties with residue structure revealed that different di-α-amino acids were not equivalent in crosslink formation. Notably, l-cystine was found to produce significantly weaker hydrogels compared to l-homocystine, l-cystathionine, and l-lanthionine, suggesting that l-cystine may be a sub-optimal choice of di-α-amino acid for preparation of copolypeptide networks. The di-α-amino acid crosslinkers also provided different chemical stability, where disulfide crosslinks were readily degraded by reduction, and thioether crosslinks were stable against reduction. This difference in response may provide a means to fine tune the reduction sensitivity of polypeptide biomaterial networks.
- Raftery, Eric D.,Gharkhanian, Eric G.,Ricapito, Nicole G.,McNamara,Deming, Timothy J.
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p. 3547 - 3553
(2018/09/25)
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- Thiabendazole-based Rh(III) and Ir(III) biscyclometallated complexes with mitochondria-targeted anticancer activity and metal-sensitive photodynamic activity
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Two pairs of Rh(III) and Ir(III) biscyclometallated complexes with thiabendazole (L1), named [Ir-a]Cl and [Rh-a]Cl, and N-benzyl-thiabendazole (L2), named [Ir-b]Cl and [Rh-b]Cl, have been designed and synthesized to explore the photophysical and biological effects that arise from changing both the metal center and the ancillary ligand. In the dark, the four metal complexes exhibit greater cytotoxicity than cisplatin against human colon (SW480) and human lung (A549) adenocarcinoma cell lines. Moreover, the pair of complexes bearing the ligand L2 is markedly more cytotoxic and present higher uptake values than complexes with L1, thereby their biological properties were studied further to determine their mechanism of action. Interestingly, in spite of the different metal center both the [Ir-b]Cl and [Rh-b]Cl complexes are responsible for the loss of mitochondrial functionality and the activation of apoptotic cell death pathways. Moreover, the photodynamic activity of the four complexes, [Ir-a,b]Cl and [Rh-a,b]Cl, was tested using visible blue light (460 nm) under soft irradiation conditions (20 min, 5.5 mW cm?2). While the Rh complexes are not photopotentiated, the phototoxicity index (IC50 non-irradiated/IC50 irradiated) of [Ir-a]Cl and [Ir-b]Cl complexes was 15.8 and 3.6, respectively. We also demonstrate that only the Ir derivatives are capable of photocatalyzing the oxidation of S-containing L-amino acids under blue light irradiation, [Ir-a]Cl being more active than [Ir-b]Cl, which provides a reasonable mechanism for their biological action (oxidative stress could be selectively promoted through a photocatalytic action) upon irradiation. This different PDT behaviour depending on the metal center and the ancillary substituent may be useful for future rational design of metal-based photosensitizers.
- Pérez-Arnaiz, Cristina,Acu?a, María Isabel,Busto, Natalia,Echevarría, Igor,Martínez-Alonso, Marta,Espino, Gustavo,García, Bego?a,Domínguez, Fernando
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supporting information
p. 279 - 293
(2018/08/17)
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- Stereoselective synthesis of lanthionine derivatives in aqueous solution and their incorporation into the peptidoglycan of Escherichia coli
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The three diastereoisomers - (R,R), (S,S) and meso - of lanthionine were synthesized in aqueous solution with high diastereoselectivity (>99%). The (S) and (R) enantiomers of two differently protected sulfamidates were opened by nucleophilic attack of (R) or (S)-cysteine. Acidification and controlled heating liberated the free lanthionines. Using the same chemistry, an α-benzyl lanthionine was also prepared. The proposed method, which avoids the need of enrichment by recrystallization, opens the way to the labelling of these compounds with 35S. Furthermore, in vivo bioincorporation into Escherichia coli W7 was studied. No incorporation of α-benzyl lanthionine was observed. In contrast, meso-lanthionine can effectively replace meso-diaminopimelic acid in vivo, while in the presence of (R,R)-lanthionine the initial increase of bacterial growth was followed by cell lysis. In the future, meso-[35S]lanthionine could be used to study the biosynthesis of peptidoglycan and its turnover in relation to cell growth and division.
- Denoel, Thibaut,Zervosen, Astrid,Gerards, Thomas,Lemaire, Christian,Joris, Bernard,Blanot, Didier,Luxen, Andre
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p. 4621 - 4628
(2014/10/16)
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- Detection of reaction intermediates during human cystathionine β-synthase-monitored turnover and H2S production
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Human cystathionine β-synthase (CBS), a novel heme-containing pyridoxal 5′-phosphate enzyme, catalyzes the condensation of homocysteine and serine or cysteine to produce cystathionine and H2O or H 2S, respectively. The presence of he
- Yadav, Pramod Kumar,Banerjee, Ruma
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p. 43464 - 43471
(2013/03/13)
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- Triply bridged (1,3,5) cyclophanes from cystine and lanthionine linkers-a comparison
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The condensation of benzene 1,3,5-tricarbonylchloride with cystine-di-Me [H2N-CH(COOMe)-CH2-S-S-CH2-CH(COOMe)-NH 2] yielded triply bridged (1,3,5) cyclophane 1, which was shown by detailed spectral studies and molecular orbital calculations to have a D3 symmetry with conformationally identical linkers and a spherical topology. In sharp contrast, the (1,3,5) cyclophane 2 from the rarely studied lanthionine di-Me [H2N-CH(COOMe)-CH2-S-CH2-CH(COOMe)-NH 2], showed only a equatorial twofold symmetry. This work highlights the special properties of the -S-S- bridge in cystine, which makes it an exceptional synthon in nature and organic synthesis.
- Ranganathan,Venkateshwarlu,Babu,Reddy,Basha,Sarma,Vijay,Sastry
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experimental part
p. 3923 - 3929
(2010/07/05)
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- Design and synthesis of dimeric HIV-1 integrase inhibitory peptides
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Dimers of known HIV-1 integrase inhibitory hexapeptide H-His-Cys-Lys-Phe-Trp-Trp-NH2 containing different lengths of cross linkers in the place of cysteine residue, were designed, and synthesized. The inhibitory potency of these dimeric peptides is consistently higher than the lead hexapeptide. The dimeric peptide with djenkolic acid linker exhibited IC50 values of 5.3 and 6.5 μM, for 3′-end processing and strand transfer, respectively.
- Krajewski, Krzysztof,Long, Ya-Qiu,Marchand, Christophe,Pommier, Yves,Roller, Peter P.
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p. 3203 - 3205
(2007/10/03)
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