83610-44-0Relevant articles and documents
Asymmetric Disulfanylbenzamides as Irreversible and Selective Inhibitors of Staphylococcus aureus Sortase A
Barthels, Fabian,Bierlmeier, Jan,Distler, Ute,Hammerschmidt, Stefan,Konh?user, Matthias,Marciniak, Tessa,Marincola, Gabriella,Schirmeister, Tanja,Schwarzer, Dirk,Tenzer, Stefan,Wich, Peter R.,Ziebuhr, Wilma
supporting information, (2020/04/22)
Staphylococcus aureus is one of the most frequent causes of nosocomial and community-acquired infections, with drug-resistant strains being responsible for tens of thousands of deaths per year. S. aureus sortase A inhibitors are designed to interfere with
Peptidomimetics for Targeting Protein-Protein Interactions between DOT1L and MLL Oncofusion Proteins AF9 and ENL
Du, Lei,Grigsby, Sierrah M.,Yao, Aihong,Chang, Yujie,Johnson, Garrett,Sun, Haiying,Nikolovska-Coleska, Zaneta
supporting information, p. 895 - 900 (2018/09/06)
MLL-fusion proteins, AF9 and ENL, play an essential role in the recruitment of DOT1L and the H3K79 hypermethylation of MLL target genes, which is pivotal for leukemogenesis. Blocking these interactions may represent a novel therapeutic approach for MLL-rearranged leukemia. Based on the 7 mer DOT1L peptide, a class of peptidomimetics was designed. Compound 21 with modified middle residues, achieved significantly improved binding affinities to AF9 and ENL, with KD values of 15 nM and 57 nM, respectively. Importantly, 21 recognizes and binds to the cellular AF9 protein and effectively inhibits the AF9-DOT1L interactions in cells. Modifications of the N- and C-termini of 21 resulted in 28 with 2-fold improved binding affinity to AF9 and much decreased peptidic characteristics. Our study provides a proof-of-concept for development of nonpeptidic compounds to inhibit DOT1L activity by targeting its recruitment and the interactions between DOT1L and MLL-oncofusion proteins AF9 and ENL.
Design, synthesis and evaluation of monovalent Smac mimetics that bind to the BIR2 domain of the anti-apoptotic protein XIAP
González-Lpez, Marcos,Welsh, Kate,Finlay, Darren,Ardecky, Robert J.,Ganji, Santhi Reddy,Su, Ying,Yuan, Hongbin,Teriete, Peter,MacE, Peter D.,Riedl, Stefan J.,Vuori, Kristiina,Reed, John C.,Cosford, Nicholas D.P.
scheme or table, p. 4332 - 4336 (2011/08/06)
We report the systematic rational design and synthesis of new monovalent Smac mimetics that bind preferentially to the BIR2 domain of the anti-apoptotic protein XIAP. Characterization of compounds in vitro (including 9i; ML101) led to the determination of key structural requirements for BIR2 binding affinity. Compounds 9h and 9j sensitized TRAIL-resistant breast cancer cells to apoptotic cell death, highlighting the value of these probe compounds as tools to investigate the biology of XIAP.
An efficient synthesis of the tamandarin B macrocycle
Lassen, Kenneth M.,Lee, Jisun,Joullié, Madeleine M.
supporting information; experimental part, p. 1635 - 1638 (2010/06/14)
A reliable, high yielding cyclization protocol for the macrocycle of tamandarin B is presented. This strategy will facilitate the synthesis of side chain analogs.
Mild one-pot conversion of carboxylic acids to amides or esters with Ph3P/trichloroisocyanuric acid
Rodrigues, Rogério Da C.,Barros, Igor M. A.,Lima, Edson L. S.
, p. 5945 - 5947 (2007/10/03)
The reaction of trichloroisocyanuric acid (TCICA) and triphenylphosphine in the presence of a carboxylic acid results in the in situ formation of the corresponding acid chloride under mild conditions. Subsequent addition of amines or alcohols, in the presence of a tertiary amine affords the corresponding amides, or esters, in good to excellent yields. The methodology was applied to the synthesis of a dipeptide.
Synthesis and kinetics of oxidation of some dipeptides with anodically generated manganese(III) sulphate: Mechanistic study
Kumara,Channe Gowda,Rangappa
, p. 438 - 444 (2007/10/03)
Dipeptides (DP) namely phenylalanyl-proline (Phe-Pro), isoleucyl-proline (Ile-Pro), and leucyl-proline (Leu-Pro) were synthesized by classical solution method and characterized. The kinetics of oxidation of these DP by Mn(III) have been studied in the presence of sulphate ions in acidic medium at 26°C. The reaction was followed spectrophotometrically at λmax = 500 nm. A first-order dependence of rate on both [Mn(III)]0 and [DP]0 was observed. The rate is independent of the concentration of reduction product, Mn(II), and hydrogen ions. The effects of varying dielectric constant of the medium and addition of anions such as sulphate, chloride, and perchlorate were studied. The activation parameters have been evaluated using Arrhenius and Eyring plots. The oxidation products were isolated and characterized. A mechanism involving the reaction of DP with Mn(III) in the rate-limiting step is suggested.
Total synthesis of dehydrodidemnin B. Use of uronium and phosphonium salt coupling reagents in peptide synthesis in solution
Jou, Gemma,Gonzalez, Isabel,Albericio, Fernando,Lloyd-Williams, Paul,Giralt, Ernest
, p. 354 - 366 (2007/10/03)
New total syntheses of didemnin A and of dehydrodidemnin B are described. The latter didemnin has the highest antiproliferative activity of all members of this family of macrocyclic depsipeptides. It was produced on coupling the side chain Pyr-Pro-OH to d
Epoxysuccinyl dipeptides as selective inhibitors of cathepsin B
Gour-Salin,Lachance,Plouffe,Storer,Menard
, p. 720 - 725 (2007/10/02)
Epoxysuccinyl dipeptide analogs of E-64 (R-EpsLeuPro-R') (Figure 1) have been synthesized with the carboxylate group on the epoxide ring either free (R = OH) or converted to an ester or an amide (R = EtO or i-BuNH) and the C- terminal amino acid proline either blocked (R' = OBzl) or free (R' = OH). These compounds were used to investigate the recently reported selectivity of this type of inhibitor for the lysosomal cysteine protease cathepsin B. It was shown that derivatization of the carboxylate on the epoxide ring confers selectivity for cathepsin B over papain only when it is combined to a dipeptidyl moiety with a free negatively charged C-terminal residue. It is proposed that this selectivity reflects interactions with histidine residues on a loop located in the primed subsites of cathepsin B which provides a positively charged anchor for the C-terminal carboxylate group of the inhibitor. The primed subsite loop of cathepsin B is not found in other cysteine proteases of the papain family and offers a unique template for designing selectivity in cysteine protease inhibitors.
Efficient total synthesis of didemnins A and B
Hamada,Kondo,Shibata,Shioiri
, p. 669 - 673 (2007/10/02)
Didemnins A and B (1 and 2), cytotoxic cyclic peptides from a Caribbean tunicate Trididemnum solidum, have been efficiently prepared by a convergent scheme from two key eastern and western fragments. Efficient routes to derivatives of the constituents of didemnis were explored. Benzyl (2RS,4S)-[O-(tert-butyldimethylsilyl)hydroxyisovaleryl]propionate (Hip derivative) was prepared from 2-hydroxyisovaleric acid by use of C-acylation of Meldrum's acid with diethyl phosphorocyanidate as a key step. Derivatives of (3S,4R,5S)-isostatine (Ist) were prepared from Boc-(R)-alloisoleucine. Methylation of Boc-(R)-Leu-OH and Z-(S)-Tyr-OH respectively afforded the corresponding N-methyl and N,O-dimethyl derivatives. The key eastern fragment, (2RS,4S)-Hip-(S)-Leu-(S)-Pro-OBzl (3), was prepared stepwise from (S)-Pro-OBzl, while Boc-(R)-MeLeu-(S)-Thr[Z-(S)-MeTyr(Me)]-(3S,4R,5S)-Ist(TBDMS)-OH (4), the key western fragment for didemnin A (1), was prepared from Ist derivatives. Coupling of 3 with 4 and cyclization, followed by deprotection, afforded didemnin A (1), which was converted to didemnin B (2).
Dielectric Relaxation Sudies on Analogues of the Polypentapeptide of Elastin
Buchet, Rene,Luan, Chi-Hao,Prasad, Kari U.,Harris, R. Dean,Urry, Dan W.
, p. 511 - 517 (2007/10/02)
Dielectric measurements of the complex permittivity of coacervate concentrations of two analogues of the polypentapeptide of elastin, (Xxx1-Pro2-Gly3-Val4-Gly5)m where Xxx is Val for the elastin polypentapeptide and Ile and Leu for the two analogues, were taken over the frequency range 1-1000 MHz and over the temperature range 0-60 degC.Two relaxation processes were observed in each polypentapeptide.One relaxation has a frequency centered in the low megahertz frequency range, which has been attributed to a low-frequency librational mode within the polypeptide.The other relaxation is located near the gigahertz frequency range.The magnitude of the dielectric increment, Δε, of the librational mode of each polypetapeptide analogue increases with increasing temperature from near zero at 0 degC to approximately 40 at 60 degC, showing an inverse temperature transition to a more ordered structure.Conversely, the magnitudes of the dielectric increment of the high-frequency relaxation decrease with increasing temperature and differ in approximate proportion to the hydrophobicity of the pentamer for the polypentapeptide of elastin and the two analogues at temperatures below the inverse temperature transition.It is suggested that clathare-like water surrounding hydrophobic side chains contributes to the high-frequency relaxation.
