14131-84-1Relevant articles and documents
Aspartic Acid Forming α-Ketoacid-Hydroxylamine (KAHA) Ligations with (S)-4,4-Difluoro-5-oxaproline
Baldauf, Simon,Bode, Jeffrey W.,Boross, Gábor N.,Ogunkoya, Ayodele O.
, (2020/02/04)
The α-ketoacid-hydroxylamine (KAHA) ligation allows the coupling of unprotected peptide segments. Currently, the most applied hydroxylamine is the 5-membered cyclic hydroxylamine (S)-5-oxaproline, which forms a homoserine ester as the primary ligation product. In order to access native aspartic acid residues at the ligation site, we synthesized a 4,4-difluoro version of this monomer. Upon KAHA ligation, the resulting difluoro alcohol hydrolyzes to an aspartic acid residue with little or no formation of aspartamide. We applied this monomer for the synthesis of the hormone peptides glucagon and an insulin variant, and as well for segment ligation of the peptides UbcH5a and SUMO3.
Synthesis of Galactosyl-Queuosine and Distribution of Hypermodified Q-Nucleosides in Mouse Tissues
Carell, Thomas,Ensfelder, Timm T.,Heiss, Matthias,Hillmeier, Markus,Kellner, Stefanie,Müller, Markus,Michalakis, Stylianos,Sch?n, Alexander,Scheel, Constanze,Thumbs, Peter,Wagner, Mirko
supporting information, p. 12352 - 12356 (2020/04/27)
Queuosine (Q) is a hypermodified RNA nucleoside that is found in tRNAHis, tRNAAsn, tRNATyr, and tRNAAsp. It is located at the wobble position of the tRNA anticodon loop, where it can interact with U as well as C bases located at the respective position of the corresponding mRNA codons. In tRNATyr and tRNAAsp of higher eukaryotes, including humans, the Q base is for yet unknown reasons further modified by the addition of a galactose and a mannose sugar, respectively. The reason for this additional modification, and how the sugar modification is orchestrated with Q formation and insertion, is unknown. Here, we report a total synthesis of the hypermodified nucleoside galactosyl-queuosine (galQ). The availability of the compound enabled us to study the absolute levels of the Q-family nucleosides in six different organs of newborn and adult mice, and also in human cytosolic tRNA. Our synthesis now paves the way to a more detailed analysis of the biological function of the Q-nucleoside family.
Discovery and Structure-Activity Relationships of Novel Template, Truncated 1′-Homologated Adenosine Derivatives as Pure Dual PPARγ/δModulators
An, Seungchan,Kim, Gyudong,Kim, Hyun Jin,Ahn, Sungjin,Kim, Hyun Young,Ko, Hyejin,Hyun, Young Eum,Nguyen, Mai,Jeong, Juri,Liu, Zijing,Han, Jinhe,Choi, Hongseok,Yu, Jinha,Kim, Ji Won,Lee, Hyuk Woo,Jacobson, Kenneth A.,Cho, Won Jea,Kim, Young-Mi,Kang, Keon Wook,Noh, Minsoo,Jeong, Lak Shin
, p. 16012 - 16027 (2021/01/09)
Following our report that A3 adenosine receptor (AR) antagonist 1 exhibited a polypharmacological profile as a dual modulator of peroxisome proliferator-activated receptor (PPAR)γ/δ, we discovered a new template, 1′-homologated adenosine analogues 4a-4t, as dual PPARγ/δmodulators without AR binding. Removal of binding affinity to A3AR was achieved by 1′-homologation, and PPARγ/δdual modulation was derived from the structural similarity between the target nucleosides and PPAR modulator drug, rosiglitazone. All the final nucleosides were devoid of AR-binding affinity and exhibited high binding affinities to PPARγ/δbut lacked PPARα binding. 2-Cl derivatives exhibited dual receptor-binding affinity to PPARγ/δ, which was absent for the corresponding 2-H derivatives. 2-Propynyl substitution prevented PPARδ-binding affinity but preserved PPARγaffinity, indicating that the C2 position defines a pharmacophore for selective PPARγligand designs. PPARγ/δdual modulators functioning as both PPARγpartial agonists and PPARδantagonists promoted adiponectin production, suggesting their therapeutic potential against hypoadiponectinemia-associated cancer and metabolic diseases.