136497-85-3Relevant articles and documents
Solid-phase parallel synthesis of functionalised medium-to-large cyclic peptidomimetics through three-component coupling driven by aziridine aldehyde dimers
Treder, Adam P.,Hickey, Jennifer L.,Tremblay, Marie-Claude J.,Zaretsky, Serge,Scully, Conor C. G.,Mancuso, John,Doucet, Annie,Yudin, Andrei K.,Marsault, Eric
, p. 9249 - 9255 (2015)
The first solid-phase parallel synthesis of macrocyclic peptides using three-component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9- to 18-membered aziridine-containing macrocycles, which are then functionalized by nucleophilic opening of the aziridine ring. This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides. Solid-phase macrocycles: The first solid-phase parallel synthesis of macrocyclic peptides using three-component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9- to 18-membered aziridine-containing macrocycles, which are then functionalised by nucleophilic opening of the aziridine ring (see scheme). This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides.
Total Synthesis of Scytonemide A Employing Weinreb AM Solid-Phase Resin
Wilson, Tyler A.,Tokarski, Robert J.,Sullivan, Peter,Demoret, Robert M.,Orjala, Jimmy,Rakotondraibe, L. Harinantenaina,Fuchs, James R.
, p. 534 - 542 (2018)
The human 20S proteasome inhibitor scytonemide A (1), a macrocyclic imine originally isolated from the cyanobacterium Scytonema hofmanni, was synthesized via a biomimetic solid-phase peptide synthesis (SPPS) approach employing the Weinreb AM resin. Utilizing this approach, cyclization of the protected heptapeptide via formation of the imine bond occurred spontaneously upon cleavage from the resin in the presence of a reducing agent and subsequent aqueous workup. The final deprotection step necessary to produce the natural product was accomplished under slightly basic conditions, facilitating cleavage of the silyl ether group while leaving the macrocycle intact. Purification of the synthetic scytonemide A was accomplished via normal-phase flash column chromatography, potentially facilitating larger scale preparation of the compound necessary for future mechanistic and SAR studies. The structure of the target compound was confirmed by NMR spectroscopy, which also shed light on differences in the spectroscopic data obtained for the synthetic and natural scytonemide A samples for some of the amide and alcohol signals in the 1H NMR spectrum.
Simplified Novel Muraymycin Analogues; using a Serine Template Strategy for Linking Key Pharmacophores
Patel, Bhautikkumar,Kerr, Rachel V,Malde, Alpeshkumar K,Zunk, Matthew,Bugg, Timothy D. H.,Grant, Gary,Rudrawar, Santosh
, p. 1429 - 1438 (2020)
The present status of antibiotic research requires the urgent invention of novel agents that act on multidrug-resistant bacteria. The World Health Organization has classified antibiotic-resistant bacteria into critical, high and medium priority according to the urgency of need for new antibiotics. Naturally occurring uridine-derived “nucleoside antibiotics” have shown promising activity against numerous priority resistant organisms by inhibiting the transmembrane protein MraY (translocase I), which is yet to be explored in a clinical context. The catalytic activity of MraY is an essential process for bacterial cell viability and growth including that of priority organisms. Muraymycins are one subclass of naturally occurring MraY inhibitors. Despite having potent antibiotic properties, the structural complexity of muraymycins advocates for simplified analogues as potential lead structures. Herein, we report a systematic structure-activity relationship (SAR) study of serine template-linked, simplified muraymycin-type analogues. This preliminary SAR lead study of serine template analogues successfully revealed that the complex structure of naturally occurring muraymycins could be easily simplified to afford bioactive scaffolds against resistant priority organisms. This study will pave the way for the development of novel antibacterial lead compounds based on a simplified serine template.
Molecular Tools for the Study of ADP-Ribosylation: A Unified and Versatile Method to Synthesise Native Mono-ADP-Ribosylated Peptides
Voorneveld, Jim,Rack, Johannes Gregor Matthias,van Gijlswijk, Luke,Meeuwenoord, Nico J.,Liu, Qiang,Overkleeft, Herman S.,van der Marel, Gijsbert A.,Ahel, Ivan,Filippov, Dmitri V.
, p. 10621 - 10627 (2021)
ADP-ribosylation (ADPr), as a post-translational modification, plays a crucial role in DNA-repair, immunity and many other cellular and physiological processes. Serine is the main acceptor for ADPr in DNA damage response, whereas the physiological impact of less common ADPr-modifications of cysteine and threonine side chains is less clear. Generally, gaining molecular insights into ADPr recognition and turn-over is hampered by the availability of homogeneous, ADP-ribosylated material, such as mono-ADP-ribosylated (MARylated) peptides. Here, a new and efficient solid-phase strategy for the synthesis of Ser-, Thr- and Cys-MARylated peptides is described. ADP-ribosylated cysteine, apart from being a native post-translational modification in its own right, proved to be suitable as a stabile bioisostere for ADP-ribosylated serine making it a useful tool to further biochemical research on serine ADP-ribosylation. In addition, it was discovered that the Streptococcus pyogenes encoded protein, SpyMacroD, acts as a Cys-(ADP-ribosyl) hydrolase.
Amino acid building blocks for efficient Fmoc solid-phase synthesis of peptides adenylylated at serine or threonine
Albers, Michael F.,Van Vliet, Bart,Hedberg, Christian
, p. 6014 - 6017 (2011)
The first straightforward building block based (non-interassembly) synthesis of peptides containing adenylylated serine and threonine residues is described. Key features include final global acidolytic protective group removal as well as full compatibility with standard Fmoc solid-phase peptide synthesis (SPPS). The described Thr-AMP SPPS-building block has been employed in the synthesis of the Thr-adenylylated sequence of human GTPase CDC42 (Ac-SEYVP-T(AMP)-VFDNYGC-NH2). Further, we demonstrate proof-of-concept for the synthesis of an Ser-adenylylated peptide (Ac-GSGA-S(AMP)-AGSGC-NH2) from the corresponding adenylylated serine building block.
Synthesis of xylose-binding cyclic octalipopeptides burkholdine-1213 analogues
Sasaki, Mio,Kadowaki, Toma,Kato, Seiya,Chida, So,Yano, Shigekazu,Nosaka, Kazuto,Konno, Hiroyuki
supporting information, (2021/11/27)
The synthesis of xylose-bearing cyclic octalipopeptides burkholdine-1213 analogues is described. Sugar-containing lipopeptides are generally highly amphiphilic and often exhibit potent antifungal activities, but a synthesis of a xylose-bearing burkholdine analogue has never been reported. We prepared burkholdine-1213 analogues by solution-phase macrolactamization of xylose-bearing linear peptides obtained by incorporating the bespoke Fmoc-Ser(β-O-xyloseAc3)-OH building block into a Fmoc-solid phase peptide synthesis protocol. All analogues synthesized exhibited similar properties and moderate antifungal activities.
Synthesis method and application of 1-aza -5-germanium-5-alkyl bicyclic [3.3.3] undecane compound.
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Paragraph 0207; 0212, (2020/05/11)
The invention provides a 1-aza-5-germanium hetero-5-alkyl bicyclic [3.3.3] hendecane compound having a structure shown in the formula I, and the types of the 1-aza-5-germanium hetero-5-alkyl bicyclic[3.3.3] hendecane compound are expanded. The provided compound can serve as a nucleophilic reagent, the air and humidity conditions of the nucleophilic reagent are stable, and the efficiency of the Ge-Stille coupling reaction of aryl halogen and the 1-aza-5-germanium hetero-5-alkyl bicyclic [3.3.3] hendecane compound is high.
An Integrated Chemical Cytometry Method: Shining a Light on Akt Activity in Single Cells
Mainz, Emilie R.,Wang, Qunzhao,Lawrence, David S.,Allbritton, Nancy L.
supporting information, p. 13095 - 13098 (2016/10/30)
Tools to evaluate oncogenic kinase activity in small clinical samples have the power to guide precision medicine in oncology. Existing platforms have demonstrated impressive insights into the activity of protein kinases, but these technologies are unsuitable for the study of kinase behavior in large numbers of primary human cells. To address these limitations, we developed an integrated analysis system that utilizes a light-programmable, cell-permeable reporter deliverable simultaneously to many cells. The reporter's ability to act as a substrate for Akt, a key oncogenic kinase, was masked by a 2-4,5-dimethoxy 2-nitrobenzyl (DMNB) moiety. Upon exposure to ultraviolet light and release of the masking moiety, the substrate sequence enabled programmable reaction times within the cell cytoplasm. When coupled to automated single-cell capillary electrophoresis, statistically significant numbers of primary human cells were readily evaluated for Akt activity.
Long-wavelength fluorescent reporters for monitoring protein kinase activity
Oien, Nathan P.,Nguyen, Luong T.,Jernigan, Finith E.,Priestman, Melanie A.,Lawrence, David S.
supporting information, p. 3975 - 3978 (2014/05/06)
In vivo optical imaging must contend with the limitations imposed by the optical window of tissue (600-1000 nm). Although a wide array of fluorophores are available that are visualized in the red and near-IR region of the spectrum, with the exception of proteases, there are few long wavelength probes for enzymes. This situation poses a particular challenge for studying the intracellular biochemistry of erythrocytes, the high hemoglobin content of which optically obscures subcellular monitoring at wavelengths less than 600 nm. To address this, tunable fluorescent reporters for protein kinase activity were developed. The probing wavelength is preprogrammed by using readily available fluorophores, thereby enabling detection within the optical window of tissue, specifically in the far-red and near-IR region. These agents were used to monitor endogenous cAMP-dependent protein kinase activity in erythrocyte lysates and in intact erythrocytes when using a light-activatable reporter. Searching far and near: Fluorescent reporters for protein kinase activity were developed. The probing wavelength is preprogrammed by using readily available fluorophores, thereby enabling detection within the optical window of tissue, specifically in the far-red and near-IR region. These agents were used to monitor endogenous cAMP-dependent protein kinase activity 1) in erythrocyte lysates and 2) in intact erythrocytes when using a light-activatable reporter.
Synthesis of the AviMeCys-containing D-ring of mersacidin
Carrillo, Angela K.,Vannieuwenhze, Michael S.
scheme or table, p. 1034 - 1037 (2012/05/07)
A chemical synthesis of the D-ring of mersacidin is reported. The synthetic route relied upon development of a method for late-stage introduction of an unusual S-[(Z)-2-aminovinyl]-(3S)-3-methyl-d-cysteine (AviMeCys) functional group via an oxidative decarbonylation/decarboxylation reaction.
