- Klíčová slova
- bioortogonální chemie,
- MeSH
- alkyny chemie MeSH
- azidy chemie MeSH
- chemické jevy MeSH
- click chemie * metody MeSH
- cykloadiční reakce klasifikace metody přístrojové vybavení MeSH
- výzkum MeSH
- Publikační typ
- přehledy MeSH
This review summarizes our work in the field of syn-thesis of natural products and their derivatives. Applica-tion of modern synthetic method is discussed in the con-text of the syntheses of both enantiomers of hydromor-phone, (–)-tetrodotoxin (a marine toxin), and selaginpul-vilins C and D (natural fluorene derivatives). Further, syn-thesis of notoincisol A, selagibenzophenones A and B is described to clarify the structural aspects of the com-pounds. Last but not least, synthesis and pharmaceutical profilation of derivatives of magnolol and honokiol is dis-cussed as well.Fulltext of this article is available on the website of this Journal.
- MeSH
- alkyny chemická syntéza chemie MeSH
- biologické přípravky MeSH
- hydromorfon chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- lignany chemická syntéza chemie MeSH
- polyacetyleny chemická syntéza chemie MeSH
- polycyklické sloučeniny chemická syntéza chemie MeSH
- Selaginellaceae chemie MeSH
- techniky syntetické chemie * metody MeSH
- tetrodotoxin chemická syntéza chemie farmakologie MeSH
- vyvíjení léků MeSH
- Check Tag
- lidé MeSH
Triacylglycerols (TAGs) containing less common fatty acids (FAs) were isolated from the seeds of three plants (Santalum album, Crepis foetida, and Leucas aspera). These FAs had allenic (laballenic acid, Lb) and acetylenic (crepenynic, C; ximenynic acids, Xi) bonds. TAGs were analyzed on reversed-phase and chiral columns. High-resolution tandem mass spectrometry identified TAGs by positive electrospray ionization (ESI+). Twenty-two molecular species of TAGs isolated from the seed oil of Santalum album were separated by RP-HPLC and chiral HPLC methods and identified by positive electrospray ionization tandem MS detection (ESI+-MS). Two major enantiomers, i.e., sn-OOLb and sn-LLLb (O represents oleic acid; and L represents linoleic acid), were synthesized from the appropriate phosphatidylcholines. This allowed the identification of enantiomers after separation by chiral chromatography by tandem mass spectrometry. Similarly, TAGs from the seeds of Crepis foetida, and Leucas aspera were analyzed by reversed-phase chromatography and identified by mass spectrometry. Four enantiomers (sn-OOC, sn-LLC, sn-OOXi, and sn-LLXi) were synthesized. A total of six and three enantiomers of TAGs containing crepenynic and ximenynic acids, respectively, were identified by chiral column analysis. The retention times of TAGs containing allenic and acetylenic bonds were always greater on the reversed-phase column than TAGs with the same number of carbon atoms and the same unsaturation (e.g., LLL versus LLLb). From the chiral column, the regioisomers and enantiomers were eluted in the order of symmetric-asymmetric-asymmetric (i.e., sn-OCO, sn-COO, and sn-OOC). Through tandem mass spectrometry, we were able to identify and distinguish regioisomer [DAG]+-type ions, i.e., [MNH4NH3RCOOH]+, that can be considered diagnostic. Unfortunately, enantiomers and TAGs with the same numbers of carbon atoms and the same unsaturation levels have identical mass spectra, such as LLL and LLLb.
- MeSH
- alkyny analýza chemie MeSH
- chromatografie kapalinová MeSH
- chromatografie s reverzní fází MeSH
- fosfatidylcholiny chemie MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- kyselina linolová analýza MeSH
- kyseliny olejové analýza MeSH
- mastné kyseliny analýza chemie MeSH
- semena rostlinná chemie MeSH
- stereoizomerie MeSH
- tandemová hmotnostní spektrometrie * MeSH
- triglyceridy analýza chemie izolace a purifikace MeSH
- vysokoúčinná kapalinová chromatografie * MeSH
- Publikační typ
- časopisecké články MeSH
To tailor cell-surface interactions, precise and controlled attachment of cell-adhesive motifs is required, while any background non-specific cell and protein adhesion has to be blocked effectively. Herein, a versatile and highly reproducible antifouling surface modification based on "clickable" groups and hierarchically structured diblock copolymer brushes for the controlled attachment of cells is reported. The polymer brush architecture combines an antifouling bottom block of poly(2-hydroxyethyl methacrylate) poly(HEMA) and an ultrathin azide-bearing top block, which can participate in well-established "click" reactions including the highly selective copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction under mild conditions. This straightforward approach allows the rapid conjugation of a cell-adhesive, alkyne-bearing cyclic RGD peptide motif, enabling subsequent specific attachment of NIH 3T3 fibroblasts, their extensive proliferation and confluent cell sheet formation after 48 h of incubation. The generally applicable strategy presented in this report can be employed for surface functionalization with diverse alkyne-bearing biological moieties via CuAAC or copper-free alkyne-azide cycloaddition protocols, making it a versatile functionalization approach and a promising tool for tissue engineering, biomaterial implant design, and other applications that require surfaces supporting highly specific cell attachment.
- MeSH
- alkyny chemie farmakologie MeSH
- antiinfekční látky chemická syntéza farmakologie MeSH
- azidy chemie farmakologie MeSH
- biokompatibilní materiály chemická syntéza farmakologie MeSH
- buňky NIH 3T3 MeSH
- click chemie MeSH
- cykloadiční reakce MeSH
- katalýza MeSH
- myši MeSH
- oligopeptidy chemie MeSH
- polyhydroxyethylmethakrylát chemie MeSH
- proliferace buněk účinky léků MeSH
- tkáňové inženýrství MeSH
- tkáňové podpůrné struktury * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cyclic pentapeptides containing the amino acid sequence arginine-glycine-aspartic (RGD) have been widely applied to target αvβ3 integrin, which is upregulated in various tumors during tumor-induced angiogenesis. Multimeric cyclic RGD peptides have been reported to be advantageous over monomeric counterparts for angiogenesis imaging. Here, we prepared mono-, di-, and trimeric cyclic arginine-glycine-aspartic-D-phenylalanine-lysine (c (RGDfK)) derivatives by conjugation with the natural chelator fusarinine C (FSC) using click chemistry based on copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC). The αvβ3 binding properties of 68Ga-labeled mono-, di-, and trimeric c(RGDfK) peptides were evaluated in vitro as well as in vivo and compared with the references monomeric [68Ga]GaNODAGA-c(RGDfK) and trimeric [68Ga]GaFSC(suc-c(RGDfK))3. All 68Ga-labeled c(RGDfK) peptides displayed hydrophilicity (logD = -2.96 to -3.80), low protein binding and were stable in phosphate buffered-saline (PBS) and serum up to 2 h. In vitro internalization assays with human melanoma M21 (αvβ3-positive) and M21-L (αvβ3-negative) cell lines showed specific uptake of all derivatives and increased in the series: mono- < di- < trimeric peptide. The highest tumor uptake, tumor-to-background ratios, and image contrast were found for the dimeric [68Ga]GaMAFC(c(RGDfK)aza)2. In conclusion, we developed a novel strategy for direct, straight forward preparation of mono-, di-, and trimeric c(RGDfK) conjugates based on the FSC scaffold. Interestingly, the best αvβ3 imaging properties were found for the dimeric [68Ga]GaMAFC(c(RGDfK)aza)2.
- MeSH
- alkyny chemie MeSH
- azidy chemie MeSH
- click chemie MeSH
- cyklické peptidy chemie farmakokinetika MeSH
- izotopové značení MeSH
- měď chemie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- PET/CT MeSH
- polymerizace MeSH
- radioizotopy galia chemie MeSH
- siderofory chemie MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
We present the application of a Glaser-Hay diyne coupling for the synthesis of conformationally constrained Nα-amino acid amides with different diyne ring sizes. Twelve-membered rings were the smallest rings that could be prepared by this approach. We observed the formation of triethylammonium adducts in the cases of smaller (10- and 11-membered) rings. Calculation of the conformational barriers for the cyclization reactions of various ring sizes demonstrated that the formation of amino acid-derived smaller rings by this reaction is thermodynamically unfavorable.
- MeSH
- alkyny chemie MeSH
- amidy chemická syntéza MeSH
- aminokyseliny chemie MeSH
- aminy chemie MeSH
- cyklizace MeSH
- diyny chemie MeSH
- katalýza MeSH
- molekulární konformace MeSH
- molekulární modely MeSH
- techniky syntézy na pevné fázi metody MeSH
- termodynamika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Advanced drug delivery systems (DDS) are easily designed following a photoiterative strategy. Multifunctional polymers are obtained by coupling building blocks of interest to an alkynated poly(ε-caprolactone) (PCL) platform via an efficient thiol-yne photoaddition. Fine-tuning over the design is achieved, as illustrated with targeting and enzyme-responsive DDS.
- MeSH
- alkyny chemie MeSH
- fotochemické procesy * MeSH
- HEK293 buňky MeSH
- kurkumin aplikace a dávkování chemie MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanostruktury aplikace a dávkování chemie MeSH
- polyestery chemie MeSH
- polyethylenglykoly chemie MeSH
- protinádorové látky aplikace a dávkování chemie MeSH
- sulfhydrylové sloučeniny chemie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The increasing popularity of peptides as promising molecular scaffolds for biomedical applications and as valuable biochemical probes makes new methods allowing for their modification highly desirable. We describe herein an optimized protocol based on a sequence of CuAAC click reactions and selective deprotection steps, which leads to an efficient multi-functionalization of synthetic peptides. The methodology has been successfully applied to the construction of defined heteroglycopeptides and fluorophore-quencher-containing probes for proteases. The developed chemistry thus represents an important addition to the available toolbox of methods enabling efficient postsynthetic modification of peptides. The commercial availability of numerous azide probes further greatly extends the application potential of the described methodology.
The rise of CuI-catalyzed click chemistry has initiated an increased demand for azido and alkyne derivatives of amino acid as precursors for the synthesis of clicked peptides. However, the use of azido and alkyne amino acids in peptide chemistry is complicated by their high cost. For this reason, we investigated the possibility of the in-house preparation of a set of five Fmoc azido amino acids: β-azido l-alanine and d-alanine, γ-azido l-homoalanine, δ-azido l-ornithine and ω-azido l-lysine. We investigated several reaction pathways described in the literature, suggested several improvements and proposed several alternative routes for the synthesis of these compounds in high purity. Here, we demonstrate that multigram quantities of these Fmoc azido amino acids can be prepared within a week or two and at user-friendly costs. We also incorporated these azido amino acids into several model tripeptides, and we observed the formation of a new elimination product of the azido moiety upon conditions of prolonged couplings with 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate/DIPEA. We hope that our detailed synthetic protocols will inspire some peptide chemists to prepare these Fmoc azido acids in their laboratories and will assist them in avoiding the too extensive costs of azidopeptide syntheses. Experimental procedures and/or analytical data for compounds 3-5, 20, 25, 26, 30 and 43-47 are provided in the supporting information. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.
An efficient and high-yielding solid phase synthesis of a small library of imidazolidin-2-ones and imidazol-2-ones was carried out employing a high chemo- and regioselective gold-catalyzed cycloisomerization as a key step. Polymer-supported amino acids derivatized with several alkyne functionalities combined with tosyl- and phenylureas have been subjected to gold-catalysis exhibiting exclusively C-N bond formation. The present work proves the potential of solid phase synthesis and homogeneous gold catalysis as an efficient and powerful synthetic tool for the generation of drug-like heterocycles.
