4817-93-0Relevant articles and documents
A Quick Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors**
Yang, Kai S.,Ma, Xinyu R.,Ma, Yuying,Alugubelli, Yugendar R.,Scott, Danielle A.,Vatansever, Erol C.,Drelich, Aleksandra K.,Sankaran, Banumathi,Geng, Zhi Z.,Blankenship, Lauren R.,Ward, Hannah E.,Sheng, Yan J.,Hsu, Jason C.,Kratch, Kaci C.,Zhao, Baoyu,Hayatshahi, Hamed S.,Liu, Jin,Li, Pingwei,Fierke, Carol A.,Tseng, Chien-Te K.,Xu, Shiqing,Liu, Wenshe Ray
supporting information, p. 942 - 948 (2020/12/15)
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital pr
Optimization and anti-cancer properties of fluoromethylketones as covalent inhibitors for ubiquitin C-terminal hydrolase L1
Chen, Hao,Das, Chittaranjan,Flaherty, Daniel P.,Galardy, Paul J.,Hewitt, Chad S.,Hussain, Sajjad,Imhoff, Ryan D.,Krabill, Aaron D.,Muli, Christine S.,Wendt, Michael K.
, (2021/05/31)
The deubiquitinating enzyme (DUB) UCHL1 is implicated in various disease states including neurodegenerative disease and cancer. However, there is a lack of quality probe molecules to gain a better understanding on UCHL1 biology. To this end a study was carried out to fully characterize and optimize the irreversible covalent UCHL1 inhibitor VAEFMK. Structure-activity relationship studies identified modifications to improve activity versus the target and a full cellular characterization was carried out for the first time with this scaffold. The studies produced a new inhibitor, 34, with an IC50 value of 7.7 μM against UCHL1 and no observable activity versus the closest related DUB UCHL3. The molecule was also capable of selectively inhibiting UCHL1 in cells and did not demonstrate any discernible off-target toxicity. Finally, the molecule was used for initial probe studies to assess the role of UCHL1 role in proliferation of myeloma cells and migration behavior in small cell lung cancer cells making 34 a new tool to be used in the biological evaluation of UCHL1.
Peptide Macrocyclization Assisted by Traceless Turn Inducers Derived from Ugi Peptide Ligation with Cleavable and Resin-Linked Amines
Puentes, Alfredo R.,Morejón, Micjel C.,Rivera, Daniel G.,Wessjohann, Ludger A.
supporting information, p. 4022 - 4025 (2017/08/15)
A multicomponent approach enabling the installation of turn-inducing moieties that facilitate the macrocyclization of short and medium-size oligopeptides is described. The strategy comprises the Ugi ligation of peptide carboxylic acids and isocyanopeptide
Fully enzymatic N→C-directed peptide synthesis using C-terminal peptide α-carboxamide to ester interconversion
Nuijens, Timo,Piva, Elena,Kruijtzer, John A. W.,Rijkers, Dirk T. S.,Liskamp, Rob M. J.,Quaedflieg, Peter J. L. M.
experimental part, p. 1039 - 1044 (2011/07/09)
Chemoenzymatic peptide synthesis is potentially the most cost-efficient technology for the synthesis of short and medium-sized peptides with some important advantages. For instance, stoichiometric amounts of expensive coupling reagents are not required and racemisation does not occur rendering purification easier compared to chemical peptide synthesis. In this paper, a novel interconversion reaction of peptide C-terminal α-carboxamides into primary alkyl esters with alcalase was used to develop a fully enzymatic peptide synthesis strategy. For each elongation step a cost-efficient amino acid carboxamide building block was used followed by the interconversion of the elongated peptide carboxamide to the corresponding primary alkyl ester. These peptide esters are the starting materials for the next enzymatic peptide elongation step. Copyright
Structures, sensory activity, and dose/response functions of 2,5-diketopiperazines in roasted cocoa nibs (Theobroma cacao)
Stark, Timo,Hofmann, Thomas
, p. 7222 - 7231 (2007/10/03)
The taste compounds inducing the blood-like, metallic bitter taste sensation reported recently for a dichloromethane extract prepared from roasted cocoa nibs were identified as a series of 25 diketopiperazines by means of HPLC degustation, LC-MS/MS, and i
Peptidic aldehydes based on α- and β-amino acids: Synthesis, inhibition of m-Calpain, and anti-cataract properties
Payne, Richard J.,Brown, Karina M.,Coxon, James M.,Morton, James D.,Lee, Hannah Yun-Young,Abell, Andrew D.
, p. 877 - 884 (2007/10/03)
We present a new synthesis of SJA6017 (a potent m-calpain inhibitor) and its adaptation in order to prepare analogues in which the constituent Leu and Val residues are systematically replaced with their corresponding β-amino acids and/or the N-terminal fl
The catalytic formation of peptide bonds with carbohydrate protein conjugates of proteases [CPC (proteases)]
Wang, Peng,Hill, Tara G.,Bednarski, Mark D.,Callstrom, Matthew R.
, p. 6827 - 6830 (2007/10/02)
This paper describes the use of carbohydrate protein conjugates of proteases [CPC(proteases)] for the catalytic formation of peptide bonds. We have found that CPC(proteases) are stable in organic solvents and perform at truly catalytic levels and have dem
KINETICS OF THE ALKALINE HYDROLYSIS OF SEVERAL N-BENZYLOXYCARBONYLDIPEPTIDE METHYL AND ETHYL ESTERS
Hoogwater, D. A.,Peereboom, M.
, p. 5325 - 5332 (2007/10/02)
The reaction rates of the alkaline hydrolysis of synthesized N-protected dipeptide methyl and ethyl esters were studied systematically.From the kinetic data the energies of activation, the pre-exponential factors and the reference values at 40 deg C were calculated.The rate of hydrolysis shows to be strongly dependent on the C-terminal amino acid in the sequence Gly >> Ala/Met/Phe > Leu >> Val/Pro.Surprisingly the N-terminal amino acid also exerts an effect, but in a different sequence.N-Terminal Phe in particular shows a relative accelerating effect.Remarkable is the significantly faster ester hydrolysis of glycine containing dipeptide ethyl esters in ethanol/water compared to the corresponding methyl esters in methanol/water.
Synthesis of Substrates of Cyclic AMP-dependent Protein Kinase and Use of Their Protected Precursors for the Convenient Preparation of Phosphoserine Peptides
Grehn, Leif,Fransson, Bengt,Ragnarsson, Ulf
, p. 529 - 536 (2007/10/02)
The synthesis of protected hexa- to nona-peptide precursors of substrates of cycylic AMP-dependent protein kinase, based on a partial amino acid sequence from rat liver pyruvate kinase, as well as of related phosphoserine peptides has been explored.A conv
