29167-28-0Relevant academic research and scientific papers
Synthesis of highly functionalized oligobenzamide proteomimetic foldamers by late stage introduction of sensitive groups
Burslem, George M.,Kyle, Hannah F.,Prabhakaran, Panchami,Breeze, Alexander L.,Edwards, Thomas A.,Warriner, Stuart L.,Nelson, Adam,Wilson, Andrew J.
, p. 3782 - 3786 (2016)
α-Helix proteomimetics represent an emerging class of ligands that can be used to inhibit an array of helix mediated protein-protein interactions. Within this class of inhibitor, aromatic oligobenzamide foldamers have been widely and successfully used. This manuscript describes alternative syntheses of these compounds that can be used to access mimetics that are challenging to synthesize using previously described methodologies, permitting access to compounds functionalized with multiple sensitive side chains and accelerated library assembly through late stage derivatisation.
Oligocarbonate molecular transporters: Oligomerization-based syntheses and cell-penetrating studies
Cooley, Christina B.,Trantow, Brian M.,Nederberg, Fredrik,Kiesewetter, Matthew K.,Hedrick, James L.,Waymouth, Robert M.,Wender, Paul A.
, p. 16401 - 16403 (2009)
(Chemical Equation Presented) A new family of guanidinium-rich molecular transporters featuring a novel oligocarbonate backbone with 1,7-side chain spacing is described. Conjugates can be rapidly assembled irrespective of length in a one-step oligomerization strategy that can proceed with concomitant introduction of probes (or by analogy drugs). The new transporters exhibit excellent cellular entry as determined by flow cytometry and fluorescence microscopy, and the functionality of their drug delivery capabilities was confirmed by the delivery of the bioluminescent small molecule probe luciferin and turnover by its intracellular target enzyme.
Conjugation of Indoles to Antibodies through a Novel Self-Immolating Linker
Dragovich, Peter S.,Blake, Robert A.,Chen, Chunjiao,Chen, Jinhua,Chuh, Josefa,den Besten, Willem,Fan, Fang,Fourie, Aimee,Hartman, Steven J.,He, Changrong,He, Jintang,Ingalla, Ellen Rei,Kozak, Katherine R.,Leong, Steven R.,Lu, Jiawei,Ma, Yong,Meng, Lingyao,Nannini, Michelle,Oeh, Jason,Ohri, Rachana,Lewis Phillips, Gail,Pillow, Thomas H.,Rowntree, Rebecca K.,Sampath, Deepak,Vandlen, Richard,Vollmar, Breanna,Wai, John,Wertz, Ingrid E.,Xu, Keyang,Xu, Zijin,Zhang, Donglu
, p. 4830 - 4834 (2018)
A novel strategy to attach indole-containing payloads to antibodies through a carbamate moiety and a self-immolating, disulfide-based linker is described. This new strategy was employed to connect a selective estrogen receptor down-regulator (SERD) to various antibodies in a site-selective manner. The resulting conjugates displayed potent, antigen-dependent down-regulation of estrogen receptor levels in MCF7-neo/HER2 and MCF7-hB7H4 cells. They also exhibited similar antigen-dependent modulation of the estrogen receptor in tumors when administered intravenously to mice bearing MCF7-neo/HER2 tumor xenografts. The indole-carbamate moiety present in the new linker was stable in whole blood from various species and also exhibited good in vivo stability properties in mice.
METHODS FOR PREPARING ANTIBODY DRUG CONJUGATES
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Page/Page column 38; 125; 126, (2018/04/21)
The subject matter described herein is directed to methods of preparing certain antibody-drug conjugates (ADCs) wherein the antibody is linked to the drug through a linker, wherein the drug contains a heteroaryl group having a secondary nitrogen, and the linker is attached to the drug via the secondary nitrogen. The resulting conjugates are useful in treating various diseases and conditions.
Tuning the molecular weight of polymeric amphiphiles as a tool to access micelles with a wide range of enzymatic degradation rates
Slor, Gadi,Papo, Nitsan,Hananel, Uri,Amir, Roey J.
supporting information, p. 6875 - 6878 (2018/06/26)
Enyzme-responsive polymeric assemblies hold great potential for biomedical applications due to the over-expression of disease-associated enzymes, which can be utilized to activate such systems only in afflicted tissues. Herein we demonstrate that the overall molecular weight of polymeric amphiphiles, which have the same hydrophilic/hydrophobic ratio, can be tuned to create polymeric micelles with an extreme range of degradation rates. This approach expands the available set of molecular parameters that can be adjusted to tune the degradation rate of polymeric assemblies, paving new possibilities for rational design of polymeric systems with controlled degradation rates.
Templated Chromophore Assembly by Dynamic Covalent Bonds
Rocard, Lou,Berezin, Andrey,De Leo, Federica,Bonifazi, Davide
supporting information, p. 15739 - 15743 (2016/01/29)
Through the simultaneous use of three orthogonal dynamic covalent reactions, namely disulfide, boronate, and acyl hydrazone formation, we conceived a facile and versatile protocol to spatially organize tailored chromophores, which absorb in the blue, red, and yellow regions, on a preprogrammed α-helix peptide. This approach allowed the assembly of the dyes in the desired ratio and spacing, as dictated by both the relative positioning and distribution of the recognition units on the peptide scaffold. Steady-state UV/Vis absorption and emission studies suggest an energy transfer from the yellow and red donors to the blue acceptor. A molecular dynamics simulation supports the experimental findings that the helical structure is maintained after the assembly and the three dyes are confined in defined conformational spaces.
NOVEL CELL-PERMEABLE SUCCINATE COMPOUNDS
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Page/Page column 71, (2015/11/03)
The present invention provides novel cell-permeable succinates and cell permeable precursors of succinate aimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane and thus the cell permeable succinates can be used to enhance mitochondrial ATP-output.
COMPOUND FOR USE IN PEPTIDE SYNTHESIS
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Page/Page column 24, (2012/02/01)
The present invention generally relates to processes and methods of peptide and protein synthesis. The present invention also relates to specific compounds for use in such processes and methods. It is shown herein that peptides with a C-terminal tertiary N,N-bis(2-mercaptoethyl)-amide (BMEA) undergo N-to-S acyl transfer at weakly acidic pH to form a transient thioester which can be captured for direct ligation with a cysteinyl peptide. These C-terminal BMEA peptides are easily prepared with standard Fmoc solid-phase synthesis protocols, thus giving a very convenient access to the thioester components for native chemical ligation.
Tandem thiol switch synthesis of peptide thioesters via N-S acyl shift on thiazolidine
Sharma, Rohit K.,Tam, James P.
supporting information; experimental part, p. 5176 - 5179 (2011/12/15)
An efficient "thiol switch" approach for the synthesis of peptide thioesters via an acid-catalyzed N-S acyl shift and a thioester exchange reaction in tandem with concurrent removal of protecting groups is described. This method employs novel 2-(thiomethyl)thiazolidine (TMT)-anchored resins and is fully compatible with Fmoc chemistry.
Peptide ligation assisted by an auxiliary attached to amidyl nitrogen
Li, Juan,Cui, Hong-Kui,Liu, Lei
scheme or table, p. 1793 - 1796 (2010/06/13)
New thiol-containing auxiliaries were developed for peptide ligation. They were placed at the amidyl N-atom in the second amino acid residue of a peptide fragment. With the new auxiliaries, peptide ligation could be conducted at non-Cys and non-Gly sites. Compared to other recently developed auxiliaries, an important feature of the present design was that the new auxiliaries were generally applicable and readily removable.
