- Supramolecular Hydrogels Respond to Ligand-Receptor Interaction
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N-(Fluorenyl-9-Methoxycarbonyl) dipeptides form supramolecular hydrogels via hydrogen bonding and hydrophobic interactions. These hydrogels respond to a ligand?receptor interaction as well as to thermal or pH perturbation and also exhibit chiral recognition. Copyright
- Zhang, Yan,Gu, Hongwei,Yang, Zhimou,Xu, Bing
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- Optimization of axial ligands to promote the photoactivation of BODIPY-conjugated platinum(iv) anticancer prodrugs
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Carboplatin-based platinum(iv) prodrugs containing axial carboxylates are relatively resistant to reduction to release active platinum(ii) species and kill cancer cells. To facilitate the activation process, a boron dipyrromethene (BODIPY) ligand has been utilized as a photoabsorber at the axial position to photoactivate carboplatin-based platinum(iv) complexes. However, the influence of the axial ligands on the photoactivation rate of the platinum center and the subsequent biological activity are still unknown. In this study, we report the design and synthesis of a series of carboplatin-based photoactivable platinum(iv) prodrugs containing BODIPY axial ligands with different lengths. The resulting BODIPY-conjugated platinum(iv) prodrugsOH2C-OH8Cbearing hydroxido ligands at the opposite axial position are slightly less stable in the dark than the corresponding prodrugsAC2C-AC8Ccontaining acetato ligands. The prodrugsOH3C-OH8Ccan be photoactivated under irradiation in eight minutes, and the photoactivation rate is further improved in prodrugsAC3C-AC8Cwhere only twenty seconds are needed. Moreover, the prodrugAC3C, in which the linker between the BODIPY photoabsorber and the platinum center has an appropriate length, is photoactivated the quickest among the acetylated prodrugsAC2C-AC8C. The high cellular accumulation may contribute more to the moderate photocytotoxicity of these prodrugs. Our research highlights the way to promote the photoactivation of BODIPY-conjugated platinum(iv) anticancer prodrugs by optimization of axial ligands and may contribute to the future rational design of photoactivable platinum-based complexes.
- Gunawan, Yuliana F.,Liu, Gongyuan,Tse, Man-Kit,Yao, Houzong,Zhu, Guangyu
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p. 13737 - 13747
(2021/10/19)
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- Site-Specific Incorporation of Multiple Thioamide Substitutions into a Peptide Backbone via Solid Phase Peptide Synthesis
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Among various peptide modification strategies, thioamide substitution by replacing the carbonyl oxygen atom of an amide bond with a sulfur atom constitutes an invaluable tool for chemical biology, for use in peptide drug discovery and protein structure-fu
- Yang, Jinhua,Wang, Changliu,Yao, Chaochao,Chen, Chunqiu,Hu, Yafang,He, Guifeng,Zhao, Junfeng
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p. 1484 - 1494
(2020/01/02)
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- Ynamide-Mediated Thiopeptide Synthesis
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Exploration of the full potential of thioamide substitution as a tool in the chemical biology of peptides and proteins has been hampered by insufficient synthetic strategies for the site-specific introduction of a thioamide bond into a peptide backbone. A novel ynamide-mediated two-step strategy for thiopeptide bond formation with readily available monothiocarboxylic acids as thioacyl donors is described. The α-thioacyloxyenamide intermediates formed from the ynamides and monothiocarboxylic acids can be purified, characterized, and stored. The balance between their activity and stability enables them to act as effective thioacylating reagents to afford thiopeptide bonds under mild reaction conditions. Amino acid functional groups such as OH, CONH2, and indole NH groups need not be protected during thiopeptide synthesis. The modular nature of this strategy enables the site-specific incorporation of a thioamide bond into peptide backbones in both solution and the solid phase.
- Yang, Jinhua,Wang, Changliu,Xu, Silin,Zhao, Junfeng
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supporting information
p. 1382 - 1386
(2019/01/08)
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- POLYCONJUGATES FOR DELIVERY OF RNAI TRIGGERS TO TUMOR CELLS IN VIVO
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The present invention is directed compositions for delivery of RNA interference (RNAi) triggers to integrin positive tumor cells in vivo. The compositions comprise RGD ligand- targeted amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or conjugate) are further covalently linked to an RNAi trigger.
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Page/Page column 36
(2015/02/25)
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- The use of a cysteinyl prolyl ester (CPE) autoactivating unit in peptide ligation reactions
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A peptide containing a cysteinyl prolyl ester (CPE) moiety at the C-terminus (CPE peptide) is spontaneously transformed into a diketopiperazine thioester via an intramolecular N-S acyl shift reaction, followed by diketopiperazine formation. The CPE peptide can be ligated with a Cys-peptide in a one-pot procedure. The peptide diketopiperazine thioester can also be transformed into a peptide thioester by intermolecular thiol-thioester exchange with external thiol compounds such as sodium mercaptoethanesulfonate. Since CPE peptides can be prepared by standard Fmoc solid-phase synthesis, it is a versatile alternative to the peptide thioester, providing a flexible ligation strategy that promises to be useful in polypeptide synthesis.
- Kawakami, Toru,Aimoto, Saburo
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body text
p. 3871 - 3877
(2009/09/30)
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- In the search for new anticancer drugs. 28. Synthesis and evaluation of highly active aminoxyl labeled amino acid derivatives containing the [N'-(2- chloroethyl)-N'-nitrosoamino]carbonyl group
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The aminoxyl (nitroxyl) labeled (2-chloroethyl)nitrosocarbamoyl (CNC) derivatives of amino acids, i.e., N-[[N'-(2-chloroethyl)-N'- nitrosoamino]carbonyl]-A-(1-oxy-2,2,6,6-tetramethylpiperidin-4-yl)amides, A = glycyl (10a), A = L-alanyl (10b), A = L-valyl (10c), A = L-phenylalanyl (10d), were synthesized and evaluated in vitro for their anticancer activities against the murine lymphocytic leukemia P388. Compounds 10a-d possessed activities ranging from 242 to 456% increase in life span (%ILS). All CDF1 male mice treated with the highly active compounds 10b and 10c at 12 mg/kg/day for 9 days were alive after 30 days. Compounds 10a-d were then tested in vivo against the murine lymphoid leukemia L1210. Compounds 10a-d exhibited, on day 60, a %ILS of 496, 663, 663, and 581, respectively. All CDF1 male mice treated with the highly active compounds 10b and 10c at 12 mg/kg/day for 9 days were alive after 60 days. The lipophilicities of compounds 10a-d were determined using the UV method. The %ILS parameters obtained against the P388 and L1210 tumor lines were correlated with the corresponding lipophilicities, and a trend was generally observed toward an increase in cytotoxicity with a concomitant decrease in hydrophobicity.
- Sosnovsky,Baysal,Erciyas
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p. 999 - 1005
(2007/10/02)
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