59524-02-6Relevant articles and documents
Switching Lysophosphatidylserine G Protein-Coupled Receptor Agonists to Antagonists by Acylation of the Hydrophilic Serine Amine
Sayama, Misa,Uwamizu, Akiharu,Ikubo, Masaya,Chen, Luying,Yan, Ge,Otani, Yuko,Inoue, Asuka,Aoki, Junken,Ohwada, Tomohiko
, p. 10059 - 10101 (2021/07/28)
Three human G protein-coupled receptors (GPCRs)—GPR34/LPS1, P2Y10/LPS2, and GPR174/LPS3—are activated specifically by lysophosphatidylserine (LysoPS), an endogenous hydrolysis product of a cell membrane component, phosphatidylserine (PS). LysoPS consists of-serine, glycerol, and fatty acid moieties connected by phosphodiester and ester linkages. We previously generated potent and selective GPCR agonists by modification of the three modules and the ester linkage. Here, we show that a novel modification of the hydrophilic serine moiety, that is, N-acylations of the serine amine, converted a GPR174 agonist to potent GPR174 antagonists. Structural exploration of the amide functionality provided access to a range of activities from agonist to partial agonist to antagonist. The present study would provide a new strategy for the development of lysophospholipid receptor antagonists.
Synthesis and antimicrobial activity of phosphonopeptide derivatives incorporating single and dual inhibitors
Anderson, Rosaleen J.,Gray, Mark,Marrs, Emma C. L.,Ng, Keng Tiong,Orenga, Sylvain,Perry, John D.
supporting information, (2020/04/10)
In diagnostic microbiology, culture media are widely used for detection of pathogenic bacteria. Such media employ various ingredients to optimize detection of specific pathogens such as chromogenic enzyme substrates and selective inhibitors to reduce the presence of commensal bacteria. Despite this, it is rarely possible to inhibit the growth of all commensal bacteria, and thus pathogens can be overgrown and remain undetected. One approach to attempt to remedy this is the use of “suicide substrates” that can target specific bacterial enzymes and selectively inhibit unwanted bacterial species. With the purpose of identifying novel selective inhibitors, six novel phosphonopeptide derivatives based on D/L-fosfalin and β-chloro-L-alanine were synthesized and tested on 19 different strains of clinically relevant bacteria. Several compounds show potential as useful selective agents that could be exploited in the recovery of several bacterial pathogens including Salmonella, Pseudomonas aeruginosa, and Listeria.
Phosphonopeptides revisited, in an era of increasing antimicrobial resistance
Anderson, Rosaleen J.,Bedernjak, Alexandre F.,Cummings, Stephen P.,Day, Kathryn M.,Gray, Mark,Jones, Amanda L.,Marrs, Emma C. L.,Perry, John D.,Varadi, Linda
supporting information, (2020/03/26)
Given the increase in resistance to antibacterial agents, there is an urgent need for the development of new agents with novel modes of action. As an interim solution, it is also prudent to reinvestigate old or abandoned antibacterial compounds to assess
PROTEIN KINASE MKK4 INHIBITORS FOR PROMOTING LIVER REGENERATION OR REDUCING OR PREVENTING HEPATOCYTE DEATH
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Page/Page column 105; 106, (2019/08/26)
The invention relates to pyrazolo-pyridine compounds which inhibit mitogen-activated protein kinase kinase 4 (MKK4) and in particular, selectively inhibit MKK4 over protein kinases JNK1 and MKK7. The compounds are useful for promoting liver regeneration or reducing or preventing hepatocyte death. They are further useful for treating osteoarthritis or rheumatoid arthritis, or CNS-related diseases.
Development of Macrocyclic Peptides Containing Epoxyketone with Oral Availability as Proteasome Inhibitors
Li, Daqiang,Zhang, Xiaotuan,Ma, Xiaodong,Xu, Lei,Yu, Jianjun,Gao, Lixin,Hu, Xiaobei,Zhang, Jiankang,Dong, Xiaowu,Li, Jia,Liu, Tao,Zhou, Yubo,Hu, Yongzhou
, p. 9177 - 9204 (2018/10/24)
Macrocyclization has been frequently utilized for optimizing peptide or peptidomimetic-based compounds. In an attempt to obtain potent, metabolically stable, and orally available proteasome inhibitors, 30 oprozomib-derived macrocyclic peptides with structural diversity in their N-terminus and linker were successively designed and synthesized for structure-activity relationship (SAR) studies. As a consequence, the macrocyclic peptides with N-methyl-pyrazole (24p, 24x), imidazole (24t), and pyrazole (24v) as their respective N-termini exhibited favorable in vitro activity and metabolic stability, which translated into their potent in vivo proteasome inhibitory activity after oral administration. In particular, compound 24v, as the most distinguished one among this series, displayed excellent chymotrypsin-like (ChT-L, β5) inhibitory potency (IC50 = 16 nM), low nanomolar antiproliferative activity against all three of the tested cell lines, and superior metabolic stability in mouse liver microsome (MLM), as well as favorable inhibition against ChT-L compared to that of oprozomib in BABL/c mice following po administration at a comparatively low dose, thereby representing a promising candidate for further development.
Straightforward synthesis of fluorinated amino acids by Michael addition of ethyl bromodifluoroacetate to α,β-unsaturated α-amino acid derivatives
Kondratov, Ivan S.,Bugera, Maxym Ya.,Tolmachova, Nataliya A.,Daniliuc, Constantin G.,Haufe, Günter
, p. 100 - 108 (2018/05/09)
Copper-mediated Michael addition of ethyl bromodifluoroacetate to N-protected α,β-unsaturated α-amino acid esters was applied for straightforward synthesis of γ,γ-difluorinated analogues of glutamic acid (compound 1) and glutamine (compound 10). Moreover, a proline-based, sterically constrained analog of γ,γ-difluoroglutamic acid (compound 24) was prepared.
Antimicrobial Compounds
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Paragraph 0114; 0115; 0171; 0172, (2017/08/26)
An antimicrobial compound, as well as the salts, derivatives and analogues thereof, said compound being represented by the general formula (I): wherein R1 represents a peptide part P1 or a peptide part P2.
New reagent for the introduction of Boc protecting group to amines: Boc-OASUD
Maheswara Rao, B. Leela,Nowshuddin, Shaik,Jha, Anjali,Divi, Murali K.,Rao
supporting information, p. 2127 - 2132 (2017/10/31)
A new reagent, tert-butyl (2,4-dioxo-3-azaspiro [5,5] undecan-3-yl) carbonate (Boc-OASUD) for the preparation of N-Boc-amino acids is described. The Boc-OASUD reacts with amino acids and their esters at room temperature in the presence of a base and gives N-Boc-amino acids and their esters in good yields and purity. Introduction of the Boc group takes place without racemization. The Boc-OASUD, being a solid and more stable, is a better alternative to di-tert-butyl dicarbonate which is low melting and has to be dispensed in plastic containers than glass because of its poor stability.
Stereoselective synthesis of lanthionine derivatives in aqueous solution and their incorporation into the peptidoglycan of Escherichia coli
Denoel, Thibaut,Zervosen, Astrid,Gerards, Thomas,Lemaire, Christian,Joris, Bernard,Blanot, Didier,Luxen, Andre
, p. 4621 - 4628 (2014/10/16)
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.
Synthesis of a novel tetrafluoropyridine-containing amino acid and tripeptide
Hudson, Alex S.,Hoose, Alex,Coxon, Christopher R.,Sandford, Graham,Cobb, Steven L.
, p. 4865 - 4867 (2013/09/02)
The synthesis of a novel fluoropyridine-containing amino acid from pentafluoropyridine by a nucleophilic substitution process is reported. The orthogonal protecting groups can be manipulated and the fluoropyridine amino acid incorporated into a tripeptide
