103321-59-1Relevant academic research and scientific papers
N-(Benzoyloxy)amines: An investigation of their thermal stability, synthesis, and incorporation into novel peptide constructs
Nemchik, Anne,Badescu, Valentina,Phanstiel IV, Otto
, p. 4315 - 4325 (2003)
A series of N-benzoyloxyamines were pyrolyzed and their decomposition temperatures correlated well with the amine architecture's ability to stabilize a N-centered radical. A variety of amine substrates were treated with a biphasic mixture of benzoyl peroxide (BPO), CH2Cl2 and an aqueous carbonate buffer (at pH 10.5). Primary and secondary amines were successfully N-benzoyloxylated in good yield. Tertiary amines and BPO gave low yields of the corresponding N-oxide and complex product mixtures, presumably via radical decomposition. Electron deficient amines (such as fluorinated aliphatic amines, α-aminoacids, α-aminoesters, and α-aminoamides) were not N-benzoyloxylated under these conditions. Instead, N-benzoylation was observed with the fluorinated amines and the reaction was sensitive to temperature and the pH of the aqueous medium. A one-pot-two-step synthesis of Nα-FMOC-L-Leu-Nβ-(benzoyloxy)-β-alanine ethyl ester, a peptide containing both an α- and a novel β-amino acid framework, was also developed.
Simultaneous fluorescent monitoring of proteasomal subunit catalysis
Wakata, Aya,Lee, Hsien-Ming,Rommel, Philipp,Toutchkine, Alexei,Schmidt, Marion,Lawrence, David S.
, p. 1578 - 1582 (2010)
The proteasome, a multicatalytic protease, displays distinct chymotrypsin-like, caspase-like, and trypsin-like activities at three different subunits of the multimeric complex. Fluorescent substrates for each of these active sites have been described. However, since the fluorescent properties of these substrates are very similar, it is not possible to simultaneously monitor catalysis of two or more activities. We have developed a long wavelength ( λex = 600 nm, λem = 700 nm) fluorescent substrate for the chymotrypsinlike active site via a combinatorial library strategy. This peptide-based substrate is a highly selective proteasomal chymotrypsin-like sensor, as assessed by a series of proteasomal active site mutants in yeast cell lysates. A corresponding caged analog of the sensor has been prepared, which is resistant to proteolysis until activated by 349 nm light. The latter affords the opportunity to assess proteasomal activity with a high degree of temporal control. The distinct photophysical properties of the sensor allow the chymotrypsin-like activity to be simultaneously monitored during caspase-like or trypsin-like catalysis. We have found that chymotrypsin-like activity is enhanced in the presence of the trypsin-like substrate but reduced in the presence of caspase-like substrate. Furthermore, the chymotrypsin-like sensor hinders the activity of both the caspase- and trypsin-like active sites. Coincident monitoring of two catalytic active sites furnishes twothirds coverage of total proteasomal activity, which should provide the means to address if and how the distinct active sites of the proteasome influence one another during catalysis.
Ring-Expansion Approach to Medium-Sized Lactams and Analysis of Their Medicinal Lead-Like Properties
Baud, Laetitia G.,Manning, Morgan A.,Arkless, Helen L.,Stephens, Thomas C.,Unsworth, William P.
, p. 2225 - 2230 (2017)
Medium-sized rings are widely considered to be under-represented in biological screening libraries for lead identification in medicinal chemistry. To help address this, a library of medium-sized lactams has been generated by using a simple, scalable and versatile ring-expansion protocol. Analysis of the library by using open-access computational tool LLAMA suggested that these lactams and their derivatives have highly promising physicochemical and 3D spatial properties and thus have much potential in drug discovery.
A New Route for the Total Synthesis of 6,7-Dihydroeponemycin
Bennacer, Bibia,Rivalle, Christian,Grierson, David S.
, p. 4569 - 4574 (2003)
A new synthesis of dihydroeponemycin (2), a peptide epoxide with potent cytotoxic and antiangiogenesis activity, has been developed. In the initial steps, Fmoc-Leu-Cl was converted into the key amino ketone intermediate 9 by Stille coupling with tributylvinyltin, conjugate addition of PhSA1Me 2 to the derived enone, S-oxidation, and heat-induced syn elimination. Subsequent reaction of 9 with H2O2 and catalytic Triton B produced the corresponding epoxides as a 1:1 diastereomeric mixture in 89 % yield. These epoxides were separated and individually converted into 2 and(2S)-epi-dihydroeponemycin (24) in a four-step "one-pot" protocol (77 % overall yield in both cases). Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
Eco-friendly synthesis of peptides using fmoc-amino acid chlorides as coupling agent under biphasic condition
Kantharaju, Kamanna,Khatavi, Santosh Y.
, p. 699 - 707 (2021/08/23)
Background: Agro-waste derived solvent media act as a greener process for the peptide bond formation using Nα-Fmoc-amino acid chloride and amino acid ester salt with in situ neutralization and coupling under biphasic condition. The Fmoc-amino acid chlorides are prepared by the reported procedure of freshly distilled SOCl2 with dry CH2Cl2. The protocol found many added ad-vantages such as neutralization of amino acid ester salt and not required additional base for the neu-tralization, and directly coupling take place with Fmoc-amino acid chloride gave final product dipeptide ester in good to excellent yields. The protocol occurs with complete stereo chemical integrity of the configuration of substrates. Here, we revisited Schotten-Baumann condition, instead of using inorganic base. Objective: To develop green protocol for the synthesis of peptide bond using Fmoc-amino acid chloride with amino acid esters salt. Methods: The final product isolated is analyzed in several spectroscopic and analytical techniques such as FT-IR,1H-,13C-NMR, Mass spectrometry and RP-HPLC to check stereo integrity and puri-ty of the product. Conclusion: The present method developed greener using natural agro-waste (lemon fruit shell ash) derived solvent medium for the reaction and not required chemical entity.
Orthogonal 19F-Labeling for Solid-State NMR Spectroscopy Reveals the Conformation and Orientation of Short Peptaibols in Membranes
Grage, Stephan L.,Kara, Sezgin,Bordessa, Andrea,Doan, Véronique,Rizzolo, Fabio,Putzu, Marina,Kuba?, Tomá?,Papini, Anna Maria,Chaume, Grégory,Brigaud, Thierry,Afonin, Sergii,Ulrich, Anne S.
supporting information, p. 4328 - 4335 (2018/02/26)
Peptaibols are promising drug candidates in view of their interference with cellular membranes. Knowledge of their lipid interactions and membrane-bound structure is needed to understand their activity and should be, in principle, accessible by solid-state NMR spectroscopy. However, their unusual amino acid composition and noncanonical conformations make it very challenging to find suitable labels for NMR spectroscopy. Particularly in the case of short sequences, new strategies are required to maximize the structural information that can be obtained from each label. Herein, l-3-(trifluoromethyl)bicyclopent[1.1.1]-1-ylglycine, (R)- and (S)-trifluoromethylalanine, and 15N-backbone labels, each probing a different direction in the molecule, have been combined to elucidate the conformation and membrane alignment of harzianin HK-VI. For the short sequence of 11 amino acids, 12 orientational constraints have been obtained by using 19F and 15N NMR spectroscopy. This strategy revealed a β-bend ribbon structure, which becomes realigned in the membrane from a surface-parallel state towards a membrane-spanning state, with increasing positive spontaneous curvature of the lipids.
A Systematic Exploration of Macrocyclization in Apelin-13: Impact on Binding, Signaling, Stability, and Cardiovascular Effects
Tran, Kien,Murza, Alexandre,Sainsily, Xavier,Coquerel, David,C?té, Jér?me,Belleville, Karine,Haroune, Lounès,Longpré, Jean-Michel,Dumaine, Robert,Salvail, Dany,Lesur, Olivier,Auger-Messier, Mannix,Sarret, Philippe,Marsault, éric
supporting information, p. 2266 - 2277 (2018/03/26)
The apelin receptor generates increasing interest as a potential target across several cardiovascular indications. However, the short half-life of its cognate ligands, the apelin peptides, is a limiting factor for pharmacological use. In this study, we systematically explored each position of apelin-13 to find the best position to cyclize the peptide, with the goal to improve its stability while optimizing its binding affinity and signaling profile. Macrocyclic analogues showed a remarkably higher stability in rat plasma (half-life >3 h versus 24 min for Pyr-apelin-13), accompanied by improved affinity (analogue 15, Ki 0.15 nM and t1/2 6.8 h). Several compounds displayed higher inotropic effects ex vivo in the Langendorff isolated heart model in rats (analogues 13 and 15, maximum response at 0.003 nM versus 0.03 nM of apelin-13). In conclusion, this study provides stable and active compounds to better characterize the pharmacology of the apelinergic system.
Synthesis and in vitro stability of amino acid prodrugs of 6-β-naltrexol for microneedle-enhanced transdermal delivery
Eldridge, Joshua A.,Milewski, Mikolaj,Stinchcomb, Audra L.,Crooks, Peter A.
, p. 5212 - 5215 (2014/12/11)
A small library of amino acid ester prodrugs of 6-β-naltrexol (NTXOL, 1) was prepared in order to investigate the candidacy of these prodrugs for microneedle-enhanced transdermal delivery. Six amino acid ester prodrugs were synthesized (6a-f). 6b, 6d, and 6e were stable enough at skin pH (pH 5.0) to move forward to studies in 50% human plasma. The lead compound (6e) exhibited the most rapid bioconversion to NTXOL in human plasma (t1/2 = 2.2 ± 0.1 h).
Synthesis of ruthenium tris(2,2′-bipyridine)-type complexes tethered to peptides at 5,5′-positions
Shiina, Yoshimi,Oishi, Shigero,Ishida, Hitoshi
supporting information; experimental part, p. 1249 - 1252 (2012/04/04)
Utilization of 5′-amino-2,2′-bipyridine-5-carboxylic acid allows molecular design of ruthenium tris(bipyridine)-type complexes bearing two different functional groups. In this study, a novel ruthenium tris(bipyridine) derivative bearing viologen and tyros
Synthetic procedure for N-Fmoc amino acyl-N-sulfanylethylaniline linker as crypto-peptide thioester precursor with application to native chemical ligation
Sakamoto, Ken,Sato, Kohei,Shigenaga, Akira,Tsuji, Kohei,Tsuda, Shugo,Hibino, Hajime,Nishiuchi, Yuji,Otaka, Akira
experimental part, p. 6948 - 6958 (2012/10/07)
N-Sulfanylethylanilide (SEAlide) peptides 1, obtainable using Fmoc-based solid-phase peptide synthesis (Fmoc SPPS), function as crypto-thioesters in native chemical ligation (NCL), yielding a wide variety of peptides/proteins. Their acylating potential with N-terminal cysteinyl peptides 2 can be tuned by the presence or absence of phosphate salts, leading to one-pot/multifragment ligation, operating under kinetically controlled conditions. SEAlide peptides have already been shown to be promising for use in protein synthesis; however, a widely applicable method for the synthesis of N-Fmoc amino acyl-N- sulfanylethylaniline linkers 4, required for the preparation of SEAlide peptides, is unavailable. The present study addresses the development of efficient condensation protocols of 20 naturally occurring amino acid derivatives to the N-sulfanylethylaniline linker 5. N-Fmoc amino acyl aniline linkers 4 of practical use in NCL chemistry, except in the case of the proline- or aspartic acid-containing linker, were successfully synthesized by coupling of POCl3- or SOCl2-activated Fmoc amino acid derivatives with sodium anilide species 6, without accompanying racemization and loss of side-chain protection. Furthermore, SEAlide peptides 7 possessing various C-terminal amino acids (Gly, His, Phe, Ala, Asn, Ser, Glu, and Val) were shown to be of practical use in NCL chemistry.
