40751-89-1Relevant articles and documents
Folding and Assembly of Short α, β, ?-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures
Zhang, Yukun,Zhong, Yulong,Connor, Alan L.,Miller, Daniel P.,Cao, Ruikai,Shen, Jie,Song, Bo,Baker, Erin S.,Tang, Quan,Pulavarti, Surya V.S.R.K.,Liu, Rui,Wang, Qiwei,Lu, Zhong-Lin,Szyperski, Thomas,Zeng, Huaqiang,Li, Xiaopeng,Smith, Richard D.,Zurek, Eva,Zhu, Jin,Gong, Bing
supporting information, p. 14239 - 14248 (2019/10/11)
Multilevel protein structures typically involve polypeptides of sufficient lengths. Here we report the folding and assembly of seven short tetrapeptides sharing the same types of α-, β-, and aromatic ?-amino acid residues. These are two sets of hybrid peptides, with three members in one set and four in the other, having complementary hydrogen-bonding sequences that were hypothesized to pair into linear H-bonded duplexes. However, instead of undergoing the anticipated pairing, the initially examined three oligomers, 1 and 2a or 2b, differing only in their central αβ hybrid dipeptide sequence, do not associate with each other and exhibit distinctly different folding behavior. Experiments based on NMR and mass spectrometry, along with computational studies and systematic inference, reveal that oligomer 1 folds into an expanded β-turn containing an unusual hybrid α/β-amino acid sequence composed of glycine and β-alanine, two α- A nd β-amino acid residues that are conformationally most flexible, and peptides 2a and 2b adopt a noncanonical, extended helical conformation and dimerize into double helices undergoing rapid conformational exchange or helix inversion. The different central dipeptide sequences, αβ vs βα, result in drastically different intramolecular H-bonding patterns that are responsible for the observed folding behavior of 1 and 2. The revealed turn and double helix have few natural or synthetic counterparts, and provide novel and unique folding prototypes based on which chiral α- A nd β-amino acids are incorporated. The resultant derivatives 1a, 1b, 2c, and 2d follow the same folding and assembling behavior and demonstrate the generality of this system with the formation of expanded β-turns and double helices with enhanced folding stabilities, hampered helix inversion, as well as defined and dominant helical sense. This work has demonstrated the unique capability of synthetic foldamers in generating structures with fascinating folding and assembling behavior. The revealed systems offer ample opportunity for further structural optimization and applications.
Synthesis and in vitro anti-platelet aggregation activities of 2-methoxy-5-arylamido-N-(pyridin-3-yl-methyl)benzamides
Wang, Yan,Wang, Xiao,Chen, Xin,Liu, Xiujie
, (2018/12/11)
In order to discover novel compounds with anti-platelet aggregation activities, a series of novel 2-methoxy-5-arylamido-N-(pyridin-3-ylmethyl)benzamides (1a–n) were synthesized and their anti-platelet aggregation activities were evaluated by the turbidimetric method in response to the following agonists: adenosine diphosphate (ADP) (5 mM/L), arachidonic acid (AA) (20 μM/L), and collagen (1 mg/mL). Those synthesized compounds that have better in vitro activities were subjected to cell toxicity tests via cell counting kit-8 (CCK-8) assay. The biological evaluation revealed that compound 1a (IC50: 0.21 μM/L) exhibited the highest anti-platelet aggregation activities when ADP was selected as an inducer, and compound 1b (IC50: 0.23 μM/L) showed the best activities when AA was selected as inducer, and compound 1m (inhibition rate: 55.06%) had significant anti-platelet aggregation activities when collagen was selected as inducer among all target compounds. Moreover, the effect of cell toxicity exhibited that none of the compounds had obvious cell toxicity against L929 cells. Therefore, 2-methoxy-5-arylamido-N-(pyridin-3-ylmethyl)benzamides have the potential to become a novel kind of anti-platelet drugs and deserve further study.
TRIAZOLONE COMPOUNDS AS mPGES-1 INHIBITORS
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Page/Page column 66, (2014/01/08)
The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.