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Search for "peptides" in Full Text gives 373 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
β-Hydroxy sulfides and their syntheses
Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143
- 80 °C, xylene; (3) TFA, CH2Cl2, followed by HPLC separation of 7 and 126. Synthesis of peptides containing a β-hydroxy sulfide moiety. Synthesis of diltiazem (12) using biocatalytic resolution of an epoxide followed by thiolysis. Acknowledgements This review was made possible by funding provided by
Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells
Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136
- potentially increases the tumor selectivity of drugs and decreases their cardiotoxicity. Increased expression of gonadotropin-releasing hormone (GnRH) receptors on the surface of tumor cells has been reported. Thus, the attachment of the aforementioned chemotherapeutic drugs to GnRH-based peptides may result
- . Small peptides that recognize target receptors on tumor cells might be suitable targeting moieties for this purpose. Hormone peptides, in particular, GnRH and somatostatin derivatives that possess antiproliferative effect on their own, are among the best candidates as homing peptides [10]. A.V. Schally
- used for amide bond formation. The difference between Dox and Dau is the lack of the primary OH group in the case of the latter one. Therefore, Dau cannot be attached to peptide carriers via an ester bond. Mtx contains a glutamic acid whose carboxyl groups are suitable for the attachment to peptides
Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions
Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116
- Anja Gronewold Mareike Horn Ines Neundorf Department of Chemistry, Biochemistry, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany 10.3762/bjoc.14.116 Abstract Within this study, we report about the design and biological characterization of novel cell-penetrating peptides (CPPs
- peptides, N50-sC18* and NrTP-sC18*, and found that they are nontoxic up to a concentration of 50 or 100 µM depending on the cell lines used. Moreover, detailed cellular uptake studies revealed that both peptides enter cells via energy-independent uptake, although endocytotic processes cannot completely
- excluded. However, initial drug delivery studies demonstrated the high versatility of these new peptides as efficient transport vectors targeting specifically nuclei and nucleoli. In future, they could be further explored as parts of newly created peptide–drug conjugates. Keywords: anticancer drugs; cell
Oligonucleotide analogues with cationic backbone linkages
Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111
- aspired improvement of cellular uptake, fully cationic oligonucleotide analogues might also be attractive candidate structures, as indicated by the advantageous properties of cationic cell-penetrating peptides (CPPs) [38]. However, the design of modifications of type 1–6 precludes the preparation of fully
Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis
Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97
- ) reagent FPID and (4-MeOC6H4)3P was successfully applied to solid-phase peptide synthesis and cyclic peptide synthesis. Four peptides with biological activities were synthesized through SPPS and the bioactive cyclic heptapeptide pseudostellarin D was obtained via solution-phase peptide synthesis. It is
- , and it plays a crucial role in the elaboration and composition of biological systems. Amide bonds are widely present not only in peptides and proteins but also in pharmaceuticals and many natural products. Among the methods for amide bond formation, the direct condensation of carboxylic acids and
- test whether the FPID/(4-MeOC6H4)3P system can be used in SPPS. We selected the commercially available 2-chlorotrityl chloride resin (2-Cl-Trt-Cl resin) as the solid support and [(9-fluorenylmethyl)oxy]carbonyl (Fmoc) as the α-amino protecting group. The peptides were synthesized following the route as
Preparation, structure, and reactivity of bicyclic benziodazole: a new hypervalent iodine heterocycle
Beilstein J. Org. Chem. 2018, 14, 1016–1020, doi:10.3762/bjoc.14.87
- and peptides [23][24][25]. Numerous examples of five-membered hypervalent iodine(III) heterocycles containing other than oxygen heteroatoms, such as sulfur [26], boron [27][28], phosphorous [29], or nitrogen [30][31][32], have been synthesized and characterized by X-ray crystallography. In particular
On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site
Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80
- throughout this review. Among the most intriguing navigating delivery systems that can combine the transporting vehicle and the navigating/targeting moiety in a single module are the tumor-homing peptides [32]. These peptides are exploited to assemble the peptide–drug conjugates (PDCs) which are considered
- attention since peptides can be easily produced in large quantities and their purification is simple. Moreover, an array of different tumor-targeting peptides has been discovered [32] for multifarious types of cancer. This bountiful palette can permit the construction of personalized cancer therapeutics
- generate the PDCs There is an immense variety of peptides (linear or cyclic) that have been exploited as carriers/targeting elements to successfully deliver the cytotoxic warhead to cancer cells [32]. These peptides are cell-specific and bind to certain receptors promoting their internalization. They are
Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property
Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78
- Vienna, Austria 10.3762/bjoc.14.78 Abstract Cyclic NGR peptides as homing devices are good candidates for the development of drug conjugates for targeted tumor therapy. In our previous study we reported that the Dau=Aoa-GFLGK(c[KNGRE]-GG-)-NH2 conjugate has a significant antitumor activity against both
- release; NGR peptides; oxime-linkage; targeted drug delivery; Introduction Targeted chemotherapy is one of the most promising approaches for selective cancer treatment that may decrease the toxic side effects of anticancer drugs. This therapeutic approach is based on the fact that tumor specific
- receptors are highly expressed on cancer cells/tissues. NGR (Asn-Gly-Arg) motif-containing peptides identified by phage display are suitable candidates for selective drug delivery. NGR peptides bind to CD13-receptors on tumor cells and tumor related angiogenic blood vessels [1][2]. CD13 is a transmembrane
Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery
Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64
- receptors (GnRH-R) [1]. Therefore, these peptides are suitable for specific drug targeting to tumor cells. The native ligand of this receptor is GnRH-I (
- , 9Pro-EA] and triporelin [6D-Trp], which are used as pharmaceutical peptides to treat inter alia hormone dependent prostate and/or breast cancer [7]. Since the mid-1980s cytotoxic GnRH-I derivatives were developed and investigated to treat tumor cells [4][5][8][9]. Anthracyclines such as doxorubicin
- pathway. To gain further information about sequence–activity relationship of GnRH-III, we studied the impact of 6Asp on the efficiency of tumor targeting. Since it is known from the literature that an incorporation of D-amino acids (D-Aaa) in position 6 of GnRH-I and II peptides can lead to an improved
Enzyme-free genetic copying of DNA and RNA sequences
Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47
- sequence long enough to hybridize stably to complementary strands were formed. Such strands may then be the templates or primers required to start enzyme-free copying. Further, the general condensation buffer noted above gave rise to the spontaneous formation of ribonucleotide- or RNA-linked peptides [64
- ]. These peptides are linked via their N-terminus to the ribonucleotide portion as phosphoramidates, which is why we refer to them as "peptido RNAs". Peptide chain growth on the 5'-phosphate is much faster than the background reaction [65], and will thus predominate over background oligomerization of amino
- considered a prebiotically relevant activating agent [67], and it has previously been used in experiments aimed at generating peptides in the absence of enzymes or a ribosomal machinery [68]. Reactions with cyanamide are much less efficient than with EDC, so that successful primer extension has not yet been
Mannich base-connected syntheses mediated by ortho-quinone methides
Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43
- were also formed in around 90% yields under microwave irradiation (Scheme 7). Miscellaneous reactions It is also known that o-QMs could cross-link two biologically important molecules such as peptides, proteins or nucleic bases. (see section Biological properties) Achieving the reaction under
Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing
Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32
- facilitate their uptake, a TAT-peptide delivery domain was conjugated to the siRNNs via A-SATE phosphotriester groups. Hence, a chimeric passenger strand containing four A-SATE phosphotriesters duplexed with an RNN guide strand was conjugated to the delivery domain TAT peptides. The resulting conjugates
- possessing only ≈25% of neutralized phosphates and four TAT peptides were optimal to enter cells passively. Once inside the cells, the SATE groups were efficiently removed by esterases, leading to siRNAs that are induced according to knockdown with apparent EC50 values in the low nanomolar range and in a
Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting
Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29
- synthetic peptides or peptidomimetics containing these sequences have been prepared and show low nanomolar IC50 values for integrin αVβ3 binding [21][22][23][24][25][26][27]. A number of cyclic RGD and isoDGR ligands containing a bifunctional diketopiperazine (DKP) scaffold have been developed by the
Photocatalytic formation of carbon–sulfur bonds
Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4
- aryl diazonium salts to give the corresponding diaryl sulfide in high yields. Very recently, Noël and co-workers applied the above-mentioned concepts for the selective arylation of cysteine and cysteine-containing peptides in batch as well as in a photomicroreactor (Scheme 18) [49]. They were able to
Aminosugar-based immunomodulator lipid A: synthetic approaches
Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3
- integrity and antigen presentation, decreases susceptibility to antimicrobial peptides and enhances pathogenicity [25]. In some LPS, the lipid A phosphates are post-translationally modified by substitution with the compounds that reduce the net negative charge of LPS, such as phosphoethanolamine in E. coli
- peptides (CAMPs) and antibiotics [25][32][33][34]. Activation of the innate immune response by lipid A/LPS requires a consecutive interaction of lipid A with lipopolysaccharide-binding protein (LPB) [35], glycosylphosphatidylinositol-anchored surface protein CD14 (a differentiation antigen of monocytes
Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles
Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2
- types of carbohydrate–protein interactions, it is therefore essential to present carbohydrates in a multivalent fashion. For that purpose, different scaffolds, such as peptides, proteins, lipids, and synthetic polymers, have all been used [7]. The search for better scaffolds for the presentation of
- system was then used for the detection of amyloid-β peptides [74], whose aggregation is responsible for Alzheimer’s disease [75]. In 2014, Fairbanks and co-workers reported a one-pot aqueous compatible method for making various triazole-linked glycoconjugates via intermediate glycosyl azides, which then
Halogen-containing thiazole orange analogues – new fluorogenic DNA stains
Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283
- been conjugated to a variety of molecules, including peptides [29], proteins [30], DNA [17], and DNA analogues such as peptide nucleic acid (PNA) [16][31]. TO-based chromophores assembled as a structural scaffold inside nucleic acids (TO-tethered nucleic acids) have attracted considerable attention [32
Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion
Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279
- of peptides as therapeutics. One strategy to increase the proteolytic stability of peptides is the modification with fluorinated amino acids. This study presents a systematic investigation of the effects of fluorinated leucine and isoleucine derivatives on the proteolytic stability of a peptide that
- was designed to comprise substrate specificities of different proteases. Therefore, leucine, isoleucine, and their side-chain fluorinated variants were site-specifically incorporated at different positions of this peptide resulting in a library of 13 distinct peptides. The stability of these peptides
- . The opposite phenomenon was observed in other cases, and this may be explained by specific interactions of fluorinated residues with the respective enzyme binding sites. Noteworthy is that 5,5,5-trifluoroisoleucine is able to significantly protect peptides from proteolysis by all enzymes included in
The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands
Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276
- drugs contain fluorine atoms or fluoroalkyl groups, representing 150 fluorinated molecules, and this trend is expected to increase to about 30% in the early future as a new generation of fluorinated compounds is currently in Phase II−III clinical trials [1]. In parallel, pharmaceutical peptides are
- attracting increasing interest as around 100 peptides are on the pharmaceutical market [2]. Peptide fluorination has appeared as a general and effective strategy to enhance the stability against enzymatic, chemical and thermal denaturation while generally retaining the original structure and biological
- activity [3][4]. Fluorinated amino acids can also be used as powerful 19F NMR probes for the study of protein–ligand interactions and enzymatic activities [5][6][7][8]. However, the development of fluorinated peptides as drug candidates seems to be largely under-exploited. Investigation on the influence of
Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres
Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262
- incorporated into peptides, it is normally necessary to first synthesize a dipeptide where the amide bond has been replaced with a monofluoroalkene. In that context, this review will present the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres described since 2007. Some
- applications of those compounds will also be presented. Keywords: dipeptide isosteres; monofluoroalkene-based amide bonds; monofluoroalkenes; peptides; synthesis; Introduction Nowadays, the pharmaceutical industry is interested in the development of new categories of drugs. While small molecules were the
- principal targets in the last decades [1], larger biomolecules, such as peptides, are now widely studied [2][3]. The interest of these biopolymers originates, in part, from their high potency and selectivity towards the target, which results in a decrease of the toxicity and/or side effects. However
Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles
Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256
- -amide bond. Furthermore, they can be used to pre-organize the amide bonds of peptides [9]. Most methods for the synthesis of tetrazoles have limitations that include multistep syntheses of starting materials and/or the use of expensive reagents. The most commonly used synthesis of 1,5-disubstituted
Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling
Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242
- predatory bacterium Herpetosiphon aurantiacus 114-95T as a test organism. This strain is capable to produce a variety of polyketides and nonribosomal peptides [13][14][15] and possesses pathways to supply specific building blocks for these natural products [16]. Furthermore, genomic analyses revealed that H
Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models
Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241
- fluorination of peptide scaffolds. One of these methods involves esterification of the C-terminus of peptides using a diazomethane species. Here, we provide an investigation of the physicochemical consequences of peptide esterification with partially fluorinated ethyl groups. Derivatives of N-acetylproline are
- undergo variable hydrolysis in biologically relevant buffers. The hydrolytic stability can be tailored over a broad pH range by varying the number of fluorine atoms in the ester moiety or by introducing adjacent charges in the peptide sequence. Keywords: conformation; ester bond; hydrolysis; peptides
- measurements can be used to study ligand–protein [12] and protein–protein interactions [13]; membrane proteins [14][15][16] and membrane-associated peptides [17][18]; equilibria among conformations of RNA [19], DNA [20], and peptide nucleic acids (PNA) [21]; and many others. Particularly recent is the
Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics
Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240
- , Bielefeld University, Universitätsstraße 25, D-33615 Bielefeld, Germany 10.3762/bjoc.13.240 Abstract The amide moiety of peptides can be replaced for example by a triazole moiety, which is considered to be bioisosteric. Therefore, the carbonyl moiety of an amino acid has to be replaced by an alkyne in
- of larger peptides. The trifluoromethyl moiety has been reported to enhance the activity, stability and selectivity of various pharmacologically active compounds [65][66], e.g., trifluridine [67][68][69][70], efavirenz [71][72][73], fluoxetine [74][75][76] and fluozolate [77]. As the general
Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis
Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228
- affect the secondary structure of peptides within which they are contained, with consequent implications for the peptides’ biological potency and selectivity [1]. A more subtle example of this concept is provided by the amino acid β-methylphenylalanine (2), which exerts conformational bias through
- acyclic means; steric interactions associated with the β-methyl group can affect the topography of peptides which once again affects the biological affinity and selectivity [2]. Extending the idea of acyclic shape control, amino acids with homologated backbones (e.g., 3–5, Figure 1) [3][4][5][6][7][8][9
- behaviour. This suggests that these fluorinated backbone-extended amino acids might enjoy future applications, for example as shape-controlled building blocks for incorporation into bioactive peptides [16]. Examples of conformationally biased amino acids [1][2][3][4][5][6][7][8][9][10]. Compound 6 is a
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