25518-33-6Relevant academic research and scientific papers
Histamine H3 receptor antagonists with peptidomimetic (keto)piperazine structures to inhibit Aβ oligomerisation
Falkenstein, Markus,Reiner-Link, David,Zivkovic, Aleksandra,Gering, Ian,Willbold, Dieter,Stark, Holger
, (2021/10/29)
Alzheime?s disease (AD) is the most prominent neurodegenerative disorder with high medical need. Protein-protein-interactions (PPI) interactions have a critical role in AD where β-amyloid structures (Aβ) build toxic oligomers. Design of disease modifying multi target directed ligand (MTDL) has been performed, which disable PPI on the one hand and on the other hand, act as procognitive antagonists at the histamine H3 receptor (H3R). The synthetized compounds are structurally based on peptidomimetic amino acid-like structures mainly as keto, diketo-, or acyl variations of a piperazine moiety connected to an H3R pharmacophore. Most of them showed low nanomolar affinities at H3R and some with promising affinity to Aβ-monomers. The structure–activity relationships (SAR) described offer new possibilities for MTDL with an optimized profile combining symptomatic and potential causal therapeutic approaches in AD.
Copper-Promoted O-Arylation of the Phenol Side Chain of Tyrosine Using Triarylbismuthines
Gagnon, Alexandre,Hébert, Martin,Le Roch, Adrien
supporting information, p. 5363 - 5367 (2020/08/27)
A general method for the O-arylation of the side chain of tyrosine using triarylbismuth reagents is reported. The reaction is mediated by copper diacetate, operates at 50 °C under oxygen in dichloromethane in the presence of pyridine, shows excellent functional group compatibility, and retains the integrity of the stereogenic center. The protocol was used to arylate the tyrosine residue of dipeptides and tripeptides.
Application of High-Throughput Competition Experiments in the Development of Aspartate-Directed Site-Selective Modification of Tyrosine Residues in Peptides
Chinn, Alex J.,Hwang, Jaeyeon,Kim, Byoungmoo,Parish, Craig A.,Krska, Shane W.,Miller, Scott J.
, p. 9424 - 9433 (2020/08/14)
Herein we report a Cu-catalyzed, site-selective functionalization of peptides that employs an aspartic acid (Asp) as a native directing motif, which directs the site of O-arylation at a proximal tyrosine (Tyr) residue. Through a series of competition studies conducted in high-throughput reaction arrays, effective conditions were identified that gave high selectivity for the proximal Tyr in Asp-directed Tyr modification. Good levels of site-selectivity were achieved in the O-arylation at a proximal Tyr residue in a number of cases, including a peptide-small molecule hybrid.
Direct modification of tripeptides using photoinduced decarboxylative radical reactions
Maeda, Kousuke,Saito, Hikaru,Osaka, Kazuyuki,Nishikawa, Keisuke,Sugie, Mai,Morita, Toshio,Takahashi, Ichiro,Yoshimi, Yasuharu
, p. 1117 - 1123 (2015/01/30)
In order to explore the applicability of photoinduced electron transfer (PET) promoted decarboxylative reactions to the direct modification of peptides, a study was performed to assess the influence of amino acid side chains on photoreactions of N-terminal protected tripeptides. Photoinduced decarboxylation reactions of tripeptides, which are composed of central amino acids that possess alkyl, phenyl, thioether, hydroxy, and amide containing side chains, in the presence or absence of acrylonitrile and a thiol were found to proceed smoothly to give the corresponding radical addition, H-abstraction, and substitution products. Although photoreactions of tripeptides containing central amino acids with phenol and indole (Tyr and Trp) moieties do not take place efficiently, appropriate protection of these groups enables the substrates to undergo smooth photoinduced decarboxylative reactions.
Tyrosine-based 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine and -adenine ((S)-HPMPC and (S)-HPMPA) prodrugs: Synthesis, stability, antiviral activity, and in vivo transport studies
Zakharova, Valeria M.,Serpi, Michaela,Krylov, Ivan S.,Peterson, Larryn W.,Breitenbach, Julie M.,Borysko, Katherine Z.,Drach, John C.,Collins, Mindy,Hilfinger, John M.,Kashemirov, Boris A.,McKenna, Charles E.
experimental part, p. 5680 - 5693 (2011/10/18)
Eight novel single amino acid (6-11) and dipeptide (12, 13) tyrosine P-O esters of cyclic cidofovir ((S)-cHPMPC, 4) and its cyclic adenine analogue ((S)-cHPMPA, 3) were synthesized and evaluated as prodrugs. In vitro IC 50 values for the prodrugs (50 0.3-35 μM); there was no cytoxicity with KB or HFF cells at ≤100 μM. The prodrugs exhibited a wide range of half-lives in rat intestinal homogenate at pH 6.5 (30-1732 min) with differences of 3-10× between phostonate diastereomers. The tyrosine alkylamide derivatives of 3 and 4 were the most stable. (l)-Tyr-NH-i-Bu cHPMPA (11) was converted in rat or mouse plasma solely to two active metabolites and had significantly enhanced oral bioavailability vs parent drug 1 in a mouse model (39% vs 5%).
Direct structural comparison of a rigid cyclic peptidic scaffold using crystallography and NMR in strained PH polymer gels
Arnusch, Christopher J.,Ippel, Johannes H.,Kooijman, Huub,Spek, Anthony L.,Liskamp, Rob M. J.,Kemmink, Johan,Pieters, Roland J.
experimental part, p. 4501 - 4507 (2010/10/02)
A small series of biaryl ether containing cyclic peptidic scaffolds was synthesized and cyclized by an SNAr reaction. The structure of one rigid scaffold was solved, by X-ray crystallography and also determined in solution by NMR spectroscopy. Molecular a
Conformationally constrained macrocycles that mimic tripeptide β-strands in water and aprotic solvents
Reid, Robert C.,Kelso, Michael J.,Scanlon, Martin J.,Fairlie, David P.
, p. 5673 - 5683 (2007/10/03)
The β-strand conformation is unknown for short peptides in aqueous solution, yet it is a fundamental building block in proteins and the crucial recognition motif for proteolytic enzymes that enable formation and turnover of all proteins. To create a gener
β-strand mimicking macrocyclic amino acids: Templates for protease inhibitors with antiviral activity
Glenn, Matthew P.,Pattenden, Leonard K.,Reid, Robert C.,Tyssen, David P.,Tyndall, Joel D. A.,Birch, Christopher J.,Fairlie, David P.
, p. 371 - 381 (2007/10/03)
New amino acids are reported in which component macrocycles are constrained to mimic tripeptides locked in a β-strand conformation. The novel amino acids involve macrocycles functionalized with both an N- and a C-terminus enabling addition of appendages a
