97885-49-9Relevant academic research and scientific papers
Novel Small Molecule-Derived, Highly Selective Substrates for Fibroblast Activation Protein (FAP)
De Decker, An,Vliegen, Gwendolyn,Van Rompaey, Dries,Peeraer, Anke,Bracke, An,Verckist, Line,Jansen, Koen,Geiss-Friedlander, Ruth,Augustyns, Koen,De Winter, Hans,De Meester, Ingrid,Lambeir, Anne-Marie,Van Der Veken, Pieter
, p. 1173 - 1179 (2019)
Fibroblast activation protein (FAP) is a proline-selective serine protease. It is hardly expressed in healthy adult tissue but upregulated in tissue remodeling sites associated with several diseases including epithelial cancer types, atherosclerosis, arthritis and fibrosis. Ongoing research aims at clinical implementation of FAP as a biomarker for these diseases. Several immunochemical methods that quantify FAP expression have been reported. An alternative/complementary approach focuses on quantification of FAP's enzymatic activity. Developing an activity-based assay for FAP has nonetheless proven challenging because of selectivity issues with respect to prolyl oligopeptidase (PREP). Here, we present substrate-type FAP probes that are structurally derived from a FAP-inhibitor (UAMC1110) that we published earlier. Both cleavage efficiency and FAP-selectivity of the best compounds in the series equal or surpass the most advanced peptide-based FAP substrates reported to date. Finally, proof-of-concept is provided that 4-aminonaphthol containing probes can spatially localize FAP activity in biological samples.
Identification of fused bicyclic derivatives of pyrrolidine and imidazolidinone as dengue virus-2 NS2B-NS3 protease inhibitors
Weng, Zhibing,Shao, Xiaoxia,Graf, Dominik,Wang, Chunguang,Klein, Christian D.,Wang, Jing,Zhou, Guo-Chun
, p. 751 - 759 (2017)
A series of fused ring derivatives of pyrrolidine and imidazolidinone were designed, synthesized, characterized and assayed against the DENV-2 NS2B-NS3 protease and wild-type DENV-2 virus. The linear dipeptide compound 1 and the non-peptidic fused ring compound 2 show comparable activities against DENV-2 NS2B-NS3 protease and wild-type DENV-2 virus in a viral replication assay. The preliminary SAR reveals that a substituent and its stereochemistry at C-3 position, substitution (X) at N-2 arene and a linker (Y) between C-3 position and its attached arene are important for the fused-ring scaffold of pyrrolidino [1,2-c]imidazolidinone to block the active site of NS2B-NS3 protease. This promising structural core will facilitate the discovery of non-peptidic, potent NS2B-NS3 protease inhibitors to stop dengue virus infections.
Recyclable Helical Poly(phenyl isocyanide)-Supported l-Proline Catalyst for Direct Asymmetric Aldol Reaction in Brine
Li, Chonglong,Wang, Jihai,Ding, Huiyun
, p. 1180 - 1190 (2020/09/07)
Abstract: A novel helical poly(phenyl isocyanide) bearing Boc protected l-proline pendants (poly-1m) was designed and synthesized. Removed the protecting Boc groups on the l-proline pendants led to the formation of helical polymer poly-2m, which showed high optical activity owing to the preferred right-handed helix of polyisocyanide main chain. Optically active helical poly-2m showed excellent catalytic ability on asymmetric aldol reaction. Helical polymer catalysts exhibited enhanced stereoselectivity in aldol reaction compared to small molecule l-proline. Under the optimized aldol reaction condition, the enantiomeric excess (ee) and diastereomeric ratio (dr) values of the aldol reaction product were respectively up to 90% and > 20/1. Moreover, the helical polyisocyanide catalyst Poly-2m can be easily recovered and reused in the aldol reaction for at least five cycles with maintained its activity and stereoselectivity. Graphic Abstract: Enantioselective aldol reaction catalyzed by poly-2m.[Figure not available: see fulltext.]
Characterisation of the aminopeptidase from non-germinated winter rape (Brassica napus L.) seeds
Kania, Joanna,Gillner, Danuta M.
, p. 180 - 186 (2016/04/19)
Rapeseed plays a crucial role in food and fuel industry. Since aminopeptidases take part in many physiological processes in all organisms, it is important to learn their role and characteristics in economically relevant plants. Extracts of non-germinated winter rape seeds were screened for aminopeptidase activity. Substrate specificity, the influence of pH and temperature, as well as effect of protease inhibitors and chosen metal ions on the aminopeptidase activity were determined. The approximate molecular weight estimated by NATIVE-PAGE and SDS-PAGE electrophoresis was ～60 kDa. The partially purified enzyme as well as the aminopeptidases present in crude extract cleaved preferentially Phe-pNA. The activity profiles toward several substrates were also determined. Maximum activity was observed at pH 6.5 and temperature of 40 °C for Phe-pNA as a substrate. Two visible picks in the pH profile toward Phe-pNA, together with other results (IEF) suggest the presence of more than one aminopeptidase, having similar molecular mass. Much lower activity and broad pH profiles were observed for Leu- and Ala-pNA as substrates.
Discovery and SAR studies of methionine-proline anilides as dengue virus NS2B-NS3 protease inhibitors
Zhou, Guo-Chun,Weng, Zhibing,Shao, Xiaoxia,Liu, Fang,Nie, Xin,Liu, Jinsong,Wang, Decai,Wang, Chunguang,Guo, Kai
supporting information, p. 6549 - 6554 (2014/01/06)
A series of methionine-proline dipeptide derivatives and their analogues were designed, synthesized and assayed against the serotype 2 dengue virus NS2B-NS3 protease, and methionine-proline anilides 1 and 2 were found to be the most active DENV 2 NS2B-NS3 competitive inhibitors with Ki values of 4.9 and 10.5 μM. The structure and activity relationship and the molecular docking revealed that l-proline, l-methionine and p-nitroaniline in 1 and 2 are the important characters in blocking the active site of NS2B-NS3 protease. Our current results suggest that the title dipeptidic scaffold represents a promising structural core to discover a new class of active NS2B-NS3 competitive inhibitors.
An efficient protocol for the amidation of carboxylic acids promoted by trimethyl phosphite and iodine
Luo, Qun-Li,Lv, Lina,Li, Yu,Tan, Jian-Ping,Nan, Wenhui,Hui, Qun
supporting information; experimental part, p. 6916 - 6922 (2012/01/06)
A practical, one-pot protocol is described for the conversion of carboxylic acids into amides through carboxyl activation by the reagent combination of trimethyl phosphite and iodine. This method integrates several advantages: (1) it allows amines to be chemoselectively acylated with excellent results in the presence of sulfur and oxygen nucleophiles; (2) the method shows wide generality in respect of solvent, base, and substrate; (3) the reagents used are widely available and much less expensive than common coupling reagents, and (4) the process is remarkably convenient, permitting extraction, recrystallization, and column chromatography as optional work-up procedures. The chemoselectivity and generality of the method, the low cost, and wide availability of reagents combined with the ease of use make it a very favorable process.
A novel chiral aliphatic-aromatic diamine promoted direct, highly enantio- and diastereoselective Michael addition of cyclohexanone to nitroolefins under solvent-free conditions
Miao, Shifeng,Bai, Jinjin,Yang, Jin,Zhang, Yawen
scheme or table, p. 855 - 862 (2010/11/17)
A series of new highly efficient chiral aliphatic-aromatic diamine catalysts have been designed and successfully applied to the asymmetric Michael addition of cyclohexanone with nitroolefins under solvent-free conditions without any acidic additives. The desired adducts were obtained in high yields with excellent enantio- and diastereoselectivities of syn products (up to >99% ee, >99:1 dr).
Secondary-secondary diamine catalysts for the enantioselective Michael addition of cyclic ketones to nitroalkenes
Pansare, Sunil V.,Kirby, Raie Lene
experimental part, p. 4557 - 4561 (2009/10/02)
Secondary-secondary diamines derived from S-proline are efficient catalysts for the ketone-nitroalkene Michael addition reaction. The stereoselectivity of the Michael addition is dependant on the pKa of the N-substituted aminomethyl pendant in
Highly diastereo- And enantioselective aldol reactions in common organic solvents using N-arylprolinamides as organocatalysts with enhanced acidity
Moorthy, Jarugu Narasimha,Saha, Satajit
experimental part, p. 739 - 748 (2009/07/19)
A broad set of N-arylprolinamides 1-8 with increasing NH acidity and steric crowding has been synthesized and its catalytic activity explored for enantioselective aldol reactions. In DMF containing 10 mol-% of TFA, all arylamides are found to catalyze the reaction between cyclohexanone and a variety of electrophilic aldehydes leading to aldols in excess of 90% yield and >95 % enantioselectivity. The per-fluorophenyl catalyst 8 is found to perform best with a broad substrate scope as compared to all other N-arylamides 1-7. It is shown that 8 can indeed be employed in highly nonpolar as well as polar solvents including brine to afford high yields of aldols with excellent diastereo- as well as enantio-selectivity. The results observed for 8 are amongst the best reported so far for prolinamides that do not contain additional stereogenic center(s) and hydrogen-bonding site(s). The molecular structures of 7 and 8, determined by X-ray crystallography and presumed to reflect the most stable conformations, reveal a notable difference in the conformations of the N-aryl rings; the aryl ring exhibits tendency to lie coplanar with the amide functionality in the case of 7, while the per- fluorophenyl ring twists almost orthogonally with respect to the plane of the amide of functionality in 8. The superior performance of the latter is attributed to, in addition to the enhanced NH acidity, the tendency of the perfluorophenyl ring to lie orthogonally to the amide group, which may facilitate a stronger binding of the electrophilic aldehyde via hydrogen bonding in the transition state.
