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1.
Thiol Michael addition reaction: a facile tool for introducing peptides into polymer‐based gene delivery systems
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Yanping Sun Hui Liu Lin Cheng Shimeng Zhu Cuifang Cai Tianzhi Yang Li Yang Pingtian Ding 《Polymer International》2018,67(1):25-31
Polymers, as widely used non‐viral gene carriers, suffer from high cytotoxicity and relatively low transfection efficiency. Such crucial drawbacks of polymers could be solved by incorporating short and bioactive peptides. The resulting synthetic polymer–peptide conjugates can not only maintain their own special characteristics, but also gain novel characteristics far beyond those of their parent polymer and peptide components to overcome barriers to gene delivery. There are various chemoselective reactions applied in the synthesis of polymer–peptide conjugates, such as Heck, Sonogashira and Suzuki coupling, Diels–Alder cycloaddition, click chemistry, Staudinger ligation, reductive alkylation and oxime/hydrazone chemistry. Among them, thiol–ene click reactions, including thiol–ene radical and thiol Michael addition reactions, are common methods for preparing peptide–polymer conjugates. In this review, we focus on thiol Michael addition reactions, elaborate on their mechanisms and highlight their applications in the synthesis of polymer–peptide conjugates for gene delivery. © 2017 Society of Chemical Industry 相似文献
2.
Donghoon Oh Dr. Shaban Anwar Darwish Dr. Amir Nasrolahi Shirazi Prof. Rakesh Kumar Tiwari Prof. Keykavous Parang 《ChemMedChem》2014,9(11):2449-2453
Two bicyclic peptides composed of tryptophan and arginine residues were synthesized from monocyclic peptide building blocks and evaluated as cellular delivery agents. [W5G]‐(triazole)‐[KR5] and [W5E]‐(β‐Ala)‐[KR5] containing triazole and β‐alanine linkers improved the cellular delivery of fluorescein (F′)‐labeled phosphopeptide F′‐GpYEEI (F′‐PP) by 7.6‐ and 19.3‐fold, respectively, in human ovarian adenocarcinoma cells. However, parent monocyclic peptide [R5] and monocyclic peptide [WR]4 only enhanced the cellular uptake of the phosphopeptide by only 1.3‐ and 3.7‐fold, respectively. Confocal microscopy showed that the corresponding fluorescein‐labeled bicyclic peptide F′‐[KW4E]‐(β‐Ala)‐[KR5] was localized in the cytosol and nucleus. Studying the cellular uptake of F′‐[KW4E]‐(β‐Ala)‐[KR5] in the presence of endocytosis inhibitors indicated that the clathrin‐ and caveolin‐dependent endocytosis are the main pathways for cellular uptake. The bicyclic peptide was able to improve antiproliferative activity of doxorubicin by 20 %. These data suggest that this bicyclic peptide can be utilized as a new class of cell‐penetrating peptides and cellular delivery tools. 相似文献
3.
Arginine Arrangement of Bacteriophage λ N‐Peptide Plays a Role as a Core Motif in GNRA Tetraloop RNA Binding
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Prof. Dr. Hiroyuki Furusawa Dr. Shinobu Fukusho Prof. Dr. Yoshio Okahata 《Chembiochem : a European journal of chemical biology》2014,15(6):865-871
A simple α‐helical N‐model‐peptide was designed to investigate the role of the arginine‐rich motif of bacteriophage λ N‐peptide in selective binding with boxB RNA. The five‐arginine arrangement of native N‐peptide was retained; all other residues were replaced with alanine. In vitro selection of RNA (30 random‐nucleotide region) was carried out with N‐model‐peptide immobilized on a 27 MHz quartz‐crystal microbalance (QCM). Selected RNAs were evaluated on the same QCM plate to obtain binding constants (Ka=107–108 M ?1). Many selected RNAs contained GNR(N)A‐type loops (similar to the boxB RNA motif recognized by the native N‐peptide). Fragments and minimal RNAs containing the GNRA‐type loop also bound to N‐model‐peptide (Ka=106–107 M ?1). The RNA recognition specificity of the peptide was studied by changing the “closing” U–A base pair and one base in the tetraloop of the RNA aptamers, and by peptide mutations (18th residue of N‐model‐peptide). It was concluded that the five‐arginine arrangement of the peptide performs selective recognition of the GNRA tetraloop and GNR(N)A pentaloop RNA structures, and that substitution of another functional amino acid residue at the 18th position in N‐peptide adds the recognition ability for a loop‐RNA sequence. 相似文献
4.
Dr. Fayçal Touti Dr. Guillaume Lautrette Kenneth D. Johnson Dr. James C. Delaney Dr. Andrew Wollacott Hamid Tissire Dr. Karthik Viswanathan Dr. Zachary Shriver Dr. Surin K. Mong Dr. Alexander J. Mijalis Dr. Obadiah J. Plante Prof. Dr. Bradley L. Pentelute 《Chembiochem : a European journal of chemical biology》2018,19(19):2039-2044
To combat antimicrobial infections, new active molecules are needed. Antimicrobial peptides, ever abundant in nature, are a fertile starting point to develop new antimicrobial agents but suffer from low stability, low specificity, and off‐target toxicity. These drawbacks have limited their development. To overcome some of these limitations, we developed antibody–bactericidal macrocyclic peptide conjugates (ABCs), in which the antibody directs the bioactive macrocyclic peptide to the targeted Gram‐negative bacteria. We used cysteine SNAr chemistry to synthesize and systematically study a library of large (>30‐mer) macrocyclic antimicrobial peptides (mAMPs) to discover variants with extended proteolytic stability in human serum and low hemolytic activity while maintaining bioactivity. We then conjugated, by using sortase A, these bioactive variants onto an Escherichia coli targeted monoclonal antibody. We found that these ABCs had minimized hemolytic activity and were able to kill E. coli at nanomolar concentrations. Our findings suggest macrocyclic peptides if fused to antibodies may facilitate the discovery of new agents to treat bacterial infections. 相似文献
5.
N′‐(2‐cyanoacetyl)acrylohydrazide (CAH) was obtained with the treatment of 2‐cyanoacetohydrazide with acryloyl chloride in acetonitrile. The obtained acrlyoyl derivative was transferred to the corresponding polymer, poly[N′‐(2‐cyanoacetyl)acrylohydrazide] (PCAH), through treatment with 2,2′‐azobisisobutyronitrile at 75°C. Copolymers with styrene or N‐phenyl acrylamide monomers were synthesized with different ratios. The structures of these polymers were characterized with elemental analysis and spectral data. The morphology, metal uptake, and ion selectivity of the polymers were studied. In addition, the swelling behavior of the polymer and metallopoymer complexes at different times of drying was also investigated. Thermogravimetric analysis of the polymer and polymer complexes under air reflected that PCAH–Pb was the most stable, followed by PCAH, PCAH–Hg, PCAH–Cu, PCAH–Ni, and PCAH–Co. A similar stability with little difference was reported under nitrogen. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 相似文献
6.
Antonio Pinto Ulrich Hoffmanns Dr. Melanie Ott Gert Fricker Prof. Dr. Nils Metzler‐Nolte Prof. Dr. 《Chembiochem : a European journal of chemical biology》2009,10(11):1852-1860
Enkephalin peptides are thought to be suitable vectors for the passage of the blood–brain barrier (BBB). Modifications that do not alter the amino acid sequence are often used to improve the permeation through living membrane systems. As a new type of modification we introduce organometallic compounds, in particular ferrocene carboxylic acid. Derivatives of [Leu5]enkephalin were synthesised and labelled with organometallic compounds by using solid‐phase synthesis techniques. All new metal–peptide bioconjugates were comprehensively characterised by HPLC, NMR spectroscopy and mass spectrometry and found to be at least 95 % pure. For the first time, permeation coefficients in a BBB model for organometal–peptide derivatives were determined in this work. The uptake and localisation of fluorescein‐labelled enkephalins was monitored by fluorescence microscopy on three cancer cell lines. Octanol/H2O partition coefficients of the compounds were measured by HPLC. The introduction of the organometallic moiety enhances the uptake into cells and the permeation coefficient of [Leu5]‐enkephalin. This could be due to an increase in lipophilicity caused by the organometallic label. The metal–peptide conjugates were found to be nontoxic up to mM concentrations. The low cytotoxicity encourages further experiments that could take advantage of the selectivity of enkephalin derivatives for opioid receptors. 相似文献
7.
Kathryn M. Johnson Michael J. Fevola Robert Y. Lochhead Charles L. McCormick 《应用聚合物科学杂志》2004,92(1):658-671
The interaction of hydrophobically modified (HM) polybetaines with selected small molecule surfactants in aqueous solution was investigated using rheological and surface tension analyses. The polymers included acrylamide‐based, HM polybetaines containing N‐butylphenylacrylamide (BPAM) and specified amounts of sulfobetaine, 3‐(2‐acrylamido‐2‐methylpropanedimethylammonio)‐1‐propanesulfonate (AMPDAPS), or carboxybetaine, 4‐(2‐acrylamido‐2‐methylpropyldimethylammonio)butanoate (AMPDAB); corresponding control (co)polymers lacking BPAM and/or betaine comonomer(s) were also examined for comparative purposes. Low charge density terpolymers exhibited greater viscosity enhancement with the addition of surfactant compared to the high charge density terpolymers. The addition of sodium dodecyl sulfate (SDS) produced the largest increase in solution viscosity, while N‐dodecyl‐N,N,N‐trimethylammonium bromide (DTAB), N‐dodecyl‐N,N‐dimethylammonio‐1‐propanesulfonate (SB3–12), and Triton X‐100 enhanced polymer solution viscosity to a lesser degree. In most cases, the high charge density carboxybetaine terpolymer exhibited diminished solution viscosity upon surfactant addition. The polymers lacking hydrophobic modification showed no detectable viscosity enhancement in the presence of surfactants. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 658–671, 2004 相似文献
8.
A series of conjugated (poly{N‐(2‐ethylhexyl)‐3,6‐carbazole–vinylene‐alt‐[(2,5‐bisphenyl)‐1,3,4‐oxadiazole]}) and nonconjugated (poly{N‐(2‐ethylhexyl)‐3,6‐carbazole–vinylene‐alt‐[(2,5‐bisphenol)‐1,3,4‐oxadiazole]}) and poly{9,9‐dihexyl‐2,7‐fluorene–vinylene‐alt‐[(2,5‐bisphenol)‐1,3,4‐oxadiazole]}) polymers containing oxadiazole and carbazole or fluorene moieties in the polymer backbone were synthesized with a multiple‐step procedure. The properties of the polymers, including the photophysical and electrochemical characteristics, could be fine‐tuned by adjustment of the components or structures in the polymer chains. The polymers were used to examine the hole‐injection/transport behavior as hole‐injection/hole‐transport layers in double‐layer indium tin oxide (ITO)/polymer/aluminum tris(8‐hydroxyquinoline)/LiF/Al devices by the determination of their energy levels. The effects of the polymers in these devices on the charge‐transport behavior were compared with a control device fabricated with poly(ethylenedioxythiophene) (PEDOT)–poly(styrene sulfonate) (PSS). Devices containing the synthesized polymers showed comparable adhesion to the ITO anode and good hole‐injection/transport performance. In addition, they exhibited higher electroluminescence over an identical range of current densities than the control device. This was attributed to the prevention of radiative exciton quenching caused by the PEDOT–PSS interfaces and the improvement of electron/exciton blocking due to the higher electron affinity of the synthesized polymers. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 相似文献
9.
Claire Minard‐Basquin Carole Chaix Franck D'Agosto Marie‐Thrse Charreyre Christian Pichot 《应用聚合物科学杂志》2004,92(6):3784-3795
A water‐soluble statistical poly(N‐acryloylmorpholine‐co‐N‐acryloxysuccinimide) [poly(NAM/NAS)] copolymer was studied for polymer–oligonucleotide (ODN) conjugate elaboration and for further use in diagnostic applications. Three different copolymers were first prepared by free‐radical solution polymerization with different N‐acryloylmorpholine (NAM) and N‐acryloxysuccinimide (NAS) molar ratios (80/20, 70/30, and 60/40). Their number‐average molecular weights ranged from 98,000 to 120,000 g/mol, as determined by aqueous size exclusion chromatography with an online light‐scattering detector. Then, polymer–ODN conjugates were obtained via a strategy consisting of the direct synthesis of ODNs onto polymer chains previously grafted onto a controlled pore glass support. Before the grafting of the polymer onto the solid support, a preliminary step was performed to bind a nucleotide starter along the polymer chain (via the reactive NAS units) to initiate automated DNA synthesis. To multiply the number of ODNs growing from starters, a branched phosphoramidite synthon [bearing two O‐dimethoxytrityl groups] was introduced at the first step of ODN elongation as a short sequence of four branched synthons alternated with three thymidine residues. Conjugates were assessed in a DNA sandwich hybridization test developed for hepatitis B virus detection. Sensitivity limits were evaluated and compared to those obtained with an other polymer, poly(maleic anhydride‐alt‐methyl vinyl ether) [poly(MA/MVE)]. A sensitivity limit of 2.6 × 107 DNA copies/mL was reached with the poly(MA/MVE)–ODN conjugate at the capture phase and with the poly(NAM/NAS)–branched ODN conjugate at the detection phase of the test. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 3784–3795, 2004 相似文献
10.
Sulfur dioxide, N,N‐diallyl‐N‐carboethoxymethylammonium chloride, and the hydrophobic monomer N,N‐diallyl‐N‐octadecylammonium chloride were cyclocopolymerized in dimethyl sulfoxide using azobisisobutyronitrile (AIBN) as the initiator to afford water‐soluble cationic polyelectrolytes (CPE) having a five‐membered cyclic structure on the polymeric backbone. The CPE on acidic hydrolysis of the pendent ester groups gave the corresponding cationic acid salts (CAS), which, on treatment with sodium hydroxide, were converted to polybetaines (PB) and anionic polyelectrolytes (APE), as well as polymers PB/APE containing various proportions of zwitterionic (PB) and anionic fractions (APE) in the polymer chain. The solution properties of the CPE, APE, and PB/APE systems containing varying amounts of the hydrophobic monomers in the range 0–4 mol % were investigated by viscometric techniques. Treating the pH‐responsive CAS polymers 4 with different equivalents of NaOH varied the zwitterionic and anionic charge densities in the polymer chain. It was found that the PB/APE polymer with a ratio of 33 : 67 for the zwitterionic and anionic fractions in the polymer chain, respectively, gave the highest viscosity value. The polymers showed that concentration (C*HA) of around 1 g/dL was required for the manifestation of significant hydrophobic associations. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1404–1411, 2005 相似文献
11.
El‐Refaie Kenawy Fouad Abdel‐Hay Mohamed El‐Newehy Raphael M Ottenbrite 《Polymer International》2008,57(1):85-91
The corresponding N‐hydroximide and N‐methyl‐N‐hydroximide of poly[ethylene‐alt‐(maleic anhydride)] (weight average molecular weight (Mw) of 100–500 g mol?1) were prepared as a new oral drug delivery system. Syntheses of N‐hydroximide and N‐methylhydroxamic acid of poly[ethylene‐alt‐(maleic anhydride)] were carried out by chemical modification of polymer with hydroxylamine and N‐methylhydroxylamine, respectively, to give water‐soluble polymers. These activated polymers were immobilized with ketoprofen in the presence of dicyclohexylcarbodiimide to give the corresponding water‐insoluble ketoprofen conjugates. All products were characterized by elemental analysis as well as Fourier transform infrared and 1H NMR spectra. In vitro release of ketoprofen was studied by measuring UV absorption at λmax = 260 nm as a function of time. This study demonstrated the potential use of N‐hydroximide and N‐methyl‐N‐hydroxamic acid of poly[ethylene‐alt‐(maleic anhydride)] as a drug delivery system. Controlled release was studied at different pH values and at different temperatures. At physiological temperature, the amount of drug released increased with increasing pH. The copolymer‐drug adducts released the drug very slowly at the low pH found in the stomach thus protecting the drug from the action of high acid conditions and resident digestive enzymes. These N‐hydroxamic acid polymer‐drug conjugates were found to be potentially useful in the delivery of macromolecular drugs to targeted sites in the lower gastrointestinal tract and the colon area. Copyright © 2007 Society of Chemical Industry 相似文献
12.
13.
Influence of the Multivalency of Ultrashort Arg‐Trp‐Based Antimicrobial Peptides (AMP) on Their Antibacterial Activity
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Barbara C. Hoffknecht Dennis J. Worm Sandra Bobersky Pascal Prochnow Prof. Dr. Julia E. Bandow Prof. Dr. Nils Metzler‐Nolte 《ChemMedChem》2015,10(9):1564-1569
Peptide dendrimers are a class of molecules of high interest in the search for new antibiotics. We used microwave‐assisted, copper(I)‐catalyzed alkyne–azide cycloaddition (CuAAC; “click” chemistry) for the simple and versatile synthesis of a new class of multivalent antimicrobial peptides (AMPs) containing solely arginine and tryptophan residues. To investigate the influence of multivalency on antibacterial activity, short solid‐phase‐ synthesized azide‐modified Arg‐Trp‐containing peptides were “clicked” to three different alkyne‐modified benzene scaffolds to access scaffolds with one, two, or three peptides. The antibacterial activity of 15 new AMPs was investigated by minimal inhibitory concentration (MIC) assays on five different bacterial strains, including a multidrug‐resistant Staphylococcus aureus (MRSA) strain. With ultrashort (2–3 residues) peptides, a clear synergistic effect of the trivalent display was observed, whereas this effect was not apparent with longer peptides. The best candidates showed activities in the low‐micromolar range against Gram‐positive MRSA. Surprisingly, the best activity against Gram‐negative Acinetobacter baumannii was observed with an ultrashort dipeptide on the trivalent scaffold (MIC: 7.5 μM ). The hemolytic activity was explored for the three most active peptides. At concentrations ten times the MIC values, <1 % hemolysis of red blood cells was observed. 相似文献
14.
Zhi Feng Dr. Yasushi Ogasawara Satoshi Nomura Prof. Dr. Tohru Dairi 《Chembiochem : a European journal of chemical biology》2018,19(19):2045-2048
MS‐271, produced by Streptomyces sp. M‐271, is a lasso peptide natural product comprising 21 amino acid residues with a d ‐tryptophan at its C terminus. Because lasso peptides are ribosomal peptides, the biosynthesis of MS‐271, especially the mechanism of d ‐Trp introduction, is of great interest. The MS‐271 biosynthetic gene cluster was identified by draft genome sequencing of the MS‐271 producer, and it was revealed that the precursor peptide contains all 21 amino acid residues including the C‐terminal tryptophan. This suggested that the d ‐Trp residue is introduced by epimerization. Genes for modification enzymes such as a macrolactam synthetase (mslC), precursor peptide recognition element (mslB1), cysteine protease (mslB2), disulfide oxidoreductases (mslE, mslF), and a protein of unknown function (mslH) were found in the flanking region of the precursor peptide gene. Although obvious epimerase genes were absent in the cluster, heterologous expression of the putative MS‐271 cluster in Streptomyces lividans showed that it contains all the necessary genes for MS‐271 production including a gene for a new peptide epimerase. Furthermore, a gene‐deletion experiment indicated that MslB1, ‐B2, ‐C and ‐H were indispensable for MS‐271 production and that some interactions of the biosynthetic enzymes were essential for the biosynthesis of MS‐271. 相似文献
15.
Dr. Haifan Wu Arusha Acharyya Dr. Yibing Wu Dr. Lijun Liu Dr. Hyunil Jo Prof. Feng Gai Prof. William F. DeGrado 《Chembiochem : a European journal of chemical biology》2018,19(9):902-906
Although helices play key roles in peptide–protein and protein–protein interactions, the helical conformation is generally unstable for short peptides (10–15 residues) in aqueous solution in the absence of their binding partners. Thus, stabilizing the helical conformation of peptides can lead to increases in binding potency, specificity, and stability towards proteolytic degradation. Helices have been successfully stabilized by introducing side chain‐to‐side chain crosslinks within the central portion of the helix. However, this approach leaves the ends of the helix free, thus leading to fraying and exposure of the non‐hydrogen‐bonded amide groups to solvent. Here, we develop a “capped‐strapped” peptide strategy to stabilize helices by embedding the entire length of the helix within a macrocycle, which also includes a semirigid organic template as well as end‐capping interactions. We have designed a ten‐residue capped‐strapped helical peptide that behaves like a miniprotein, with a cooperative thermal unfolding transition and Tm≈70 °C, unprecedented for helical peptides of this length. The NMR structure determination confirmed the design, and X‐ray crystallography revealed a novel quaternary structure with implications for foldamer design. 相似文献
16.
Zero–zero‐birefringence polymers which exhibit no orientational birefringence and no photoelastic birefringence may be suitable candidates for the components of optical devices. To develop zero–zero‐birefringence polymers, a novel copolymerization system is required. We investigated two types of birefringence of poly(N‐methylmaleimide) (PMeMI) and showed that PMeMI exhibits positive orientational and photoelastic birefringence. On the basis of the results, we calculated the optimal composition for compensating both types of birefringence by solving three equations which describe the relationship between birefringence properties and weight fraction of monomers. When the copolymer compositions were MMA/BzMA/MeMI = 86/8/6 and 88/8/4 (wt %), zero–zero‐birefringence polymers were obtained. By using MeMI as a comonomer, these zero–zero‐birefringence polymers have a much higher glass transition temperature (Tg) than those of previous researches. Also, this polymer film has high transparency comparable with that of PMMA film. Therefore, we conclude that we successfully prepared zero–zero‐birefringence polymers using N‐substituted maleimide and that N‐substituted maleimide is a promising material for zero–zero‐birefringence polymers for optical devices. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40423. 相似文献
17.
Protein Arginine N‐Methyltransferase Substrate Preferences for Different Nη‐Substituted Arginyl Peptides
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Dylan Thomas Timo Koopmans Dr. Ted M. Lakowski Helmi Kreinin Mynol I. Vhuiyan Shona A. Sedlock Dr. Jennifer M. Bui Dr. Nathaniel I. Martin Dr. Adam Frankel 《Chembiochem : a European journal of chemical biology》2014,15(11):1607-1613
Protein arginine N‐methyltransferases (PRMTs) catalyze methyl‐group transfer from S‐adenosyl‐L ‐methionine onto arginine residues in proteins. In this study, modifications were introduced at the guanidine moiety of a peptidyl arginine residue to investigate how changes to the PRMT substrate can modulate enzyme activity. We found that peptides bearing Nη‐hydroxy or Nη‐amino substituted arginine showed higher apparent kcat values than for the monomethylated substrate when using PRMT1, whereas this catalytic preference was not observed for PRMT4 and PRMT6. Methylation by compromised PRMT1 variants E153Q and D51N further supports the finding that the N‐hydroxy substitution facilitates methyl transfer by tuning the reactivity of the guanidine moiety. In contrast, Nη‐nitro and Nη‐canavanine substituted substrates inhibit PRMT activity. These findings demonstrate that methylation of these PRMT substrates is dependent on the nature of the modification at the guanidine moiety. 相似文献
18.
Cellular Antisense Activity of PNA–Oligo(bicycloguanidinium) Conjugates Forming Self‐Assembled Nanoaggregates
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Dr. Julián Valero Dr. Takehiko Shiraishi Prof. Javier de Mendoza Prof. Peter E. Nielsen 《Chembiochem : a European journal of chemical biology》2015,16(11):1593-1600
A series of peptide nucleic acid–oligo(bicycloguanidinium) (PNA–BGn) conjugates were synthesized and characterized in terms of cellular antisense activity by using the pLuc750HeLa cell splice correction assay. PNA–BG4 conjugates exhibited low micromolar antisense activity, and their cellular activity required the presence of a hydrophobic silyl terminal protecting group on the oligo(BG) ligand and a minimum of four guanidinium units. Surprisingly, a nonlinear dose–response with an activity threshold around 3–4 μM , indicative of large cooperativity, was observed. Supported by light scattering and electron microscopy analyses, we propose that the activity, and thus cellular delivery, of these lipo‐PNA–BG4 conjugates is dependent on self‐assembled nanoaggregates. Finally, cellular activity was enhanced by the presence of serum. Therefore we conclude that the lipo‐BG‐PNA conjugates exhibit an unexpected mechanism for cell delivery and are of interest for further in vivo studies. 相似文献
19.
The antifolate‐type anticancer drug methotrexate (MTX) has for many years, in numerous laboratories, been a “workhorse” drug for conjugation with natural and synthetic macromolecular carriers for the purpose of enhancing bioavailability and lowering toxic side effects. In the project here described the polymer–drug conjugation strategy is utilized for the preparation of water‐soluble polyaspartamide–methotrexate conjugates in which the drug is carrier‐anchored through short spacers containing ester groups as biofissionable links. To this end, polyaspartamide carriers 1, poly‐α,β‐D,L ‐N‐(2‐hydroxyethyl)aspartamide, and 2, poly‐α,β‐D,L ‐N‐[2‐(2‐hydroxyethoxy)ethyl]aspartamide, are treated with MTX in DMF solution in the presence of a carbodiimide coupling agent and 4‐(dimethylamino)pyridine catalyst. The molar MTX/OH feed ratios, 0.28 and lower, are chosen in these coupling reactions so as to provide conjugates featuring drug‐loading levels in the approximate range of 3–16 mol % MTX, roughly corresponding to 6–28% by mass. The water‐soluble product polymers are purified by aqueous dialysis, collected in the solid state by freeze‐drying, and structurally characterized by 1H–NMR spectroscopy. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 1844–1849, 2001 相似文献
20.
Elżbieta Megiel 《应用聚合物科学杂志》2013,127(6):4858-4864
The ketone functionalized N‐alkoxyamine, a derivative of 4‐oxo‐2,2,6,6‐tetramethylpiperidin‐1‐oxyl (4‐oxo‐TEMPO) was synthesized and applied as an initiator in the nitroxide mediated polymerization of styrene in bulk at 120°C. In the presence of the prepared initiator: 1‐phenyl‐1‐(4‐oxo‐2,2,6,6‐tetramethylpiperidinoxy)propanone polymers with well‐defined molecular weight were obtained. By contrast, when an accelerator such as acetic anhydride (10%) was added to the system, lower control of polymerization was observed. Additionally, the functionality of polymers was evaluated on the basis of a quantitative investigation of UV–visible spectra of 2,4‐dinitrophenylhydrazone formed from the polymers and the synthesized initiator. The UV–vis spectra of the hydrazone derivatives obtained from polymers by means of 2,4‐dinitrophenylhydrazone made it possible to confirm that the polymers prepared in the presence of the ketone functionalized N‐alkoxyamine retain the ketone functionality on the polymer chain. The functionality for the obtained polymers exceeded 1 significantly. The obtained (α, ω) telechelic polymers are of great importance in the synthesis of new biohybrid materials such as bioconjugates with proteins or peptides as well as new polymer nanostructures. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013 相似文献