99938-68-8Relevant articles and documents
Site-Selective Thiolation of (Multi)halogenated Heteroarenes
Sandfort, Frederik,Knecht, Tobias,Pinkert, Tobias,Daniliuc, Constantin G.,Glorius, Frank
, p. 6913 - 6919 (2020/05/14)
A general and simple strategy for the site-selective thiolation of various pharmaceutically relevant electron-rich heteroarenes with thiols is reported. This mild and reliable photocatalytic protocol enables C-S coupling at the most electron-rich position of the (multi)halogenated substrates, complementing established methodologies. Experimental and computational studies suggest a radical chain mechanism with the key step being a homolytic aromatic substitution of the heteroaryl halide by an electrophilic thiyl radical, highlighting an underdeveloped reactivity mode.
A Genetically Encoded, Phage-Displayed Cyclic-Peptide Library
Wang, Xiaoshan Shayna,Chen, Peng-Hsun Chase,Hampton, J. Trae,Tharp, Jeffery M.,Reed, Catrina A.,Das, Sukant K.,Wang, Duen-Shian,Hayatshahi, Hamed S.,Shen, Yang,Liu, Jin,Liu, Wenshe Ray
supporting information, p. 15904 - 15909 (2019/10/28)
Superior to linear peptides in biological activities, cyclic peptides are considered to have great potential as therapeutic agents. To identify cyclic-peptide ligands for therapeutic targets, phage-displayed peptide libraries in which cyclization is achieved by the covalent conjugation of cysteines have been widely used. To resolve drawbacks related to cysteine conjugation, we have invented a phage-display technique in which its displayed peptides are cyclized through a proximity-driven Michael addition reaction between a cysteine and an amber-codon-encoded N?-acryloyl-lysine (AcrK). Using a randomized 6-mer library in which peptides were cyclized at two ends through a cysteine–AcrK linker, we demonstrated the successful selection of potent ligands for TEV protease and HDAC8. All selected cyclic peptide ligands showed 4- to 6-fold stronger affinity to their protein targets than their linear counterparts. We believe this approach will find broad applications in drug discovery.
Aldehyde-mediated bioconjugation: Via in situ generated ylides
Parmar, Sangeeta,Pawar, Sharad P.,Iyer, Ramkumar,Kalia, Dimpy
, p. 14926 - 14929 (2019/12/24)
A technically simple approach for rapid, high-yielding and site-selective bioconjugation has been developed for both in vitro and cellular applications. This method involves the generation of maleimido-phosphonium ylides via 4-nitrophenol catalysis under physiological conditions followed by their Wittig reactions with aldehyde-appended biomolecules.
A Bifunctional Spin Label for Ligand Recognition on Surfaces
Hollas, Michael A.,Webb, Simon J.,Flitsch, Sabine L.,Fielding, Alistair J.
, p. 9449 - 9453 (2017/08/01)
In situ monitoring of biomolecular recognition, especially at surfaces, still presents a significant technical challenge. Electron paramagnetic resonance (EPR) of biomolecules spin-labeled with nitroxides can offer uniquely sensitive and selective insights into these processes, but new spin-labeling strategies are needed. The synthesis and study of a bromoacrylaldehyde spin label (BASL), which features two attachment points with orthogonal reactivity is reported. The first examples of mannose and biotin ligands coupled to aqueous carboxy-functionalized gold nanoparticles through a spin label are presented. EPR spectra were obtained for the spin-labeled ligands both free in solution and attached to nanoparticles. The labels were recognized by the mannose-binding lectin, Con A, and the biotin-binding protein avidin-peroxidase. Binding gave quantifiable changes in the EPR spectra from which binding profiles could be obtained that reflect the strength of binding in each case.
Intracellular Delivery of Functional Proteins and Native Drugs by Cell-Penetrating Poly(disulfide)s
Fu, Jiaqi,Yu, Changmin,Li, Lin,Yao, Shao Q.
, p. 12153 - 12160 (2015/10/06)
The efficient delivery of bioactive compounds into cells is a major challenge in drug discovery. We report herein the development of novel methods for intracellular delivery of functional proteins (including antibodies) and native small-molecule drugs by
REACTIVITY-BASED SCREENING FOR NATURAL PRODUCT DISCOVERY
-
, (2016/01/01)
A method of identifying a natural product comprising NP-[X]n is provided. The method includes several steps. The first step includes selecting an organism having a biosynthetic pathway for producing the natural product comprising NP-[X]n/
Reduction with tris(2-carboxyethyl)phosphine (TCEP) enables the use of an S-sulphonate protecting group for thiol-mediated bioconjugation
Maret, Barbara,Regnier, Thomas,Rossi, Jean-Christophe,Garrelly, Laurent,Vial, Laurent,Pascal, Robert
, p. 7725 - 7728 (2014/02/14)
Herein, we demonstrate the effectiveness of the water-friendly S-sulphonate group as an alternative to traditional thiol protecting groups for subsequent deprotection-bioconjugation reactions, under conditions that are compatible with the use of biochemic
Advanced aqueous-phase phosphoramidation reactions for effectively synthesizing peptide-oligonucleotide conjugates trafficked into a human cell line
Wang, Tzu-Pin,Ko, Ni Chien,Su, Yu-Chih,Wang, Eng-Chi,Severance, Scott,Hwang, Chi-Ching,Shih, Ying Ting,Wu, Min Hui,Chen, Yen-Hsu
, p. 2417 - 2433 (2013/02/23)
Peptide-oligonucleotide conjugates (POCs) have held promise as effective therapeutic agents in treating microbial infections and human genetic diseases including cancers. In clinical applications, POCs are especially useful to circumvent cellular delivery and specificity problems of oligonucleotides. We previously reported that nucleic acid phosphoramidation reactions performed in aqueous solutions have the potential for facile POC synthesis. Here, we carried out further studies to significantly improve aqueous-phase two-step phosphoramidation reaction yield. Optimized reactions were employed to effectively synthesize POCs for delivery into human A549 cells. We achieved optimization of aqueous-phase two-step phosphoramidation reaction and improved reaction yield by (1) determining appropriate co-solutes and co-solute concentrations to acquire higher reaction yields, (2) exploring a different nucleophilicity of imidazole and its derivatives to stabilize essential nucleic acid phosphorimidazolide intermediates prior to POC formation, and (3) enhancing POC synthesis by increasing reactant nucleophilicity. The advanced two-step phosphoramidation reaction was exploited to effectively conjugate a well-studied cell penetrating peptide, the Tat48-57 peptide, with oligonucleotides, bridged by either no linkers or a disulfide-containing linker, to have the corresponding POC yields of 47-75%. Phosphoramidation-synthesized POCs showed no cytotoxicity to human A549 cells at studied POC concentrations after 24 h inoculation and were successfully trafficked into the human A549 cell line as demonstrated by flow cytometry, fluorescent microscopy, and confocal laser scanning microscopy study. The current report provides insight into aqueous-phase phosphoramidation reactions, the knowledge of which was used to develop effective strategies for synthesizing POCs with crucial applications including therapeutic agents for medicine.
Synthesis and biological evaluation of molecular probes based on the 9-methylstreptimidone derivative DTCM-glutarimide
Ota, Eisuke,Takeiri, Masatoshi,Tachibana, Miyuki,Ishikawa, Yuichi,Umezawa, Kazuo,Nishiyama, Shigeru
scheme or table, p. 164 - 167 (2012/03/10)
Molecular probes based on 3-[(dodecylthiocarbonyl)methyl]glutarimide (DTCM-glutarimide) were synthesized and assessed for inhibitory activity against LPS-induced NO production. Among the probes examined, several derivatives exhibited potential for use in determining the target proteins of DTCM-glutarimide.
Bio-functionalized gold nanoparticles for surface-plasmon-absorption-based protein detection
Kim, Wan-Joong,Choi, Soo-Hee,Rho, Young S.,Yoo, Dong Jin
experimental part, p. 4171 - 4175 (2012/03/26)
Bio-functionalized gold nanoparticles (AuNPs), which bio-specifically interact with biotin-(strept)avidin, were investigated in this study. AuNPs were functionalized with a synthetically-provided biotin-linked thiol (BLT), which was synthesized by amidati
