Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• mechanistic considerations are highlighted in the text when appropriate. Keywords: C–H functionalisation; heterocycles; late-stage functionalisation; medicinal chemistry; organic dyes; organic photocatalysts; peptide chemistry; photoredox catalysis; Review 1 Introduction 1.1 Main advantages of

• Peptide-type linkages Medicinal chemists often draw inspiration from nature for the design of their molecules. With the exception of certain natural products, most naturally occurring biologically active molecules contain amides. The formation of the amide functional group is the most utilised reaction in

• structural characteristic of peptides is the disulfide bridge formed by cysteines. This functional group is much more prevalent in peptide medicinal chemistry. Noël et al. have published a protocol for the aerobic oxidation of thiols to disulfides, using Eosin Y photocatalysis and TMEDA (Scheme 3) [43]. The

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• publications have been reported about receptors that more effectively interact with less charged nucleotides. For instance, Kuchelmeister et al. synthesized a receptor with two symmetric peptide arms decorated with guanidinium-based anion binding sites. This receptor showed a stronger binding of AMP in

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• bioactivities and/or functions, which has been one of the central topics in the field of chemical biology [16][17][18][19][20][21][22][23][24][25][26]. Since peptide synthesis and oligonucleotide synthesis require different chemistries, such conjugations are typically carried out in the latter stages of the

• linkages that can be formed between native functional groups would be safe alternatives, and are known as natural conjugates such as nucleopeptides and nucleolipids [49]. We have been developing alkyl chain soluble support (ACSS)-assisted liquid-phase methods, specifically for peptide and oligonucleotide

• supported reactants would be unique alternatives that allow the use of unactivated amino acids or nucleosides. In peptide synthesis, activation of the N-terminus is rather rare, except for some recent encouraging examples [62][63][64][65][66][67][68]; however, this is not the case for oligonucleotide

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• from p-nitrophenyl α-D-mannopyranoside (1), which was first reduced to the corresponding amine 6 [26][27] by catalytic hydrogenation (Scheme 1). HATU-mediated peptide coupling with Boc-protected glycine under basic conditions led to 7. After removal of the Boc protecting group using trifluoroacetic

• acid in water, the resulting crude product was subjected to a subsequent peptide-coupling reaction employing the carboxy-functionalized diazirine 8. Diazirine 8 was prepared in a nine-step synthesis according to the literature [28]. For the synthesis of ligand 4, mannoside 6 was first converted into

• the squaric acid monoester 10 employing squaric acid diester 9. The monoester 10 was reacted with N-Boc-ethylendiamine to obtain the squaric acid diamide 11. Then removal of the Boc protecting group with trifluoroacetic acid followed by peptide coupling with the diazirine 8 led to target molecule 4

A hemicryptophane with a triple-stranded helical structure

• Augustin Long,
• Olivier Perraud,
• Erwann Jeanneau,
• Christophe Aronica,
• Jean-Pierre Dutasta and
• Alexandre Martinez

Beilstein J. Org. Chem. 2018, 14, 1885–1889, doi:10.3762/bjoc.14.162

• parallel peptide chains coil about each other in a triple stranded left-handed helical structure. Its high thermal and mechanical stability results mainly from the numerous hydrogen bonds found in the triple helix framework [2]. Bioinspired structures, based on peptide backbones, have been built, allowing

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• significant attention as a potential antivirulence alternative to traditional antibiotics. Streptococcus pneumoniae, a notorious human pathogen responsible for a variety of acute and chronic infections, utilizes the competence regulon and its associated signaling peptide, the competence stimulating peptide

• (CSP), to acquire antibiotic resistance and establish an infection. In this work, we sought to define the binding pockets within the ComD1 receptor used for binding the hydrophobic side-chain residues in CSP1 through the introduction of highly-conservative point mutations within the peptide

• stimulating peptide (CSP); protein–peptide interactions; quorum sensing; Streptococcus pneumoniae; structure–activity relationships (SAR); Introduction Quorum sensing (QS), a cell-density mechanism utilized by bacteria to assess their population density through the detection of diffusible signal molecules

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• , once incorporated into targeted cancer cells thanks to the multivalent platform. Keywords: anticancer drug; calixarene; cell targeting; RGD peptide; ruthenium complex; Introduction Long-living luminescent polyazaaromatic ruthenium(II) complexes are intensively studied in a biological context, in

• polyarginine [34][35][36][37]. The tethering of a photoreactive RuII complex on the transactivating transcriptional activator (TAT) peptide was also reported and it was shown that the corresponding RuII conjugate could be internalized inside HeLa cells without any modification of the photochemical properties

• anchoring i) of the photoreactive [Ru(TAP)2phen]2+ complex on the calix[4]arene small rim through a peptide-type coupling and ii) of the four c-[RGDfK] moieties on the opposite rim through a copper-catalyzed azide–alkyne cycloaddition (CuAAC) [66][67][68] (Figure 1). It was thus necessary to block the calix

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• show that both a natural antimicrobial peptide (AMP) derived from wasp venom (decoralin, Dec-NH2), and its synthetic variants generated via peptide design, display potent activity against cancer cells. We tested the derivatives at increasing doses and observed anticancer activity at concentrations as

• low as 12.5 μmol L−1 for the selective targeting of MCF-7 breast cancer cells. Flow cytometry assays further revealed that treatment with wild-type (WT) peptide Dec-NH2 led to necrosis of MCF-7 cells. Additional atomic force microscopy (AFM) measurements indicated that the roughness of cancer cell

• membranes increased significantly when treated with lead peptides compared to controls. Biophysical features such as helicity, hydrophobicity, and net positive charge were identified to play an important role in the anticancer activity of the peptides. Indeed, abrupt changes in peptide hydrophobicity and

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

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• , Nagyvárad tér 4., Budapest, 1089, Hungary University of Konstanz, Department of Chemistry and Zukunftskolleg, Universitätsstrasse 10, 78467 Konstanz, Germany Eötvös Loránd University, Faculty of Science, Institute of Chemistry, Pázmány P. stny 1/A Budapest, 1117, Hungary MTA-ELTE Research Group of Peptide

• : cardiotoxicity; drug targeting; GnRH-conjugates; HCM; HUVEC; impedimetry; Introduction Gonadotropin-releasing hormone (GnRH) is a peptide hormone secreted by the hypothalamus, which stimulates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary. Thus, it represents

• ]. These side effects can limit the applicability of these chemotherapeutic drugs. The conjugation of doxorubicin and daunorubicin to a GnRH-III-based targeting peptide could lead to decreased cardiotoxic effect through the more specific drug targeting. Drug delivery systems containing doxorubicin

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• ) with selective suborganelle-targeting properties. The nuclear localization sequence N50, as well as the nucleoli-targeting sequence NrTP, respectively, were fused to a shortened version of the cell-penetrating peptide sC18. We examined cellular uptake, subcellular fate and cytotoxicity of these novel

• 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

• direct penetration. The latter is described for those cases, where only small cargos are attached to the CPP [11]. We have designed a cell-penetrating peptide sequence, namely sC18, which we efficiently used in previous studies as drug transporter [12][13][14][15][16][17]. sC18 is composed of the last 16

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• linkages, with the nucleic acid mimic 'peptide nucleic acid' (PNA) [11][12][13] representing a striking example. Although the achiral PNA backbone is pronouncedly different from native nucleic acid structures, PNAs are capable of sequence-specific hybridization to native nucleic acids. However, their

• moderate water solubility and peptide-like folding properties [9] are hurdles for their biological application. As an alternative strategy, the (deoxy)ribose part of the backbone has been retained and only some of the internucleotide phosphate diesters have been selectively replaced by electroneutral

• peptide synthesis using the monomeric 3'-amino-nucleosyl amino acids (S)-56 and (R)-56, respectively, as building blocks. The synthesis of thymidinyl amino acids 56 was again started from a corresponding 5'-aldehyde 57 using Wittig–Horner olefination and catalytic asymmetric hydrogenation as key steps

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• Cryptophycins are natural occurring cyclic depsipeptides that were first isolated from cyanobacteria Nostoc sp. ATCC 53789 in 1990 [1]. Cryptophycins target tubulin, in particular the peptide site of the vinca domain. They block microtubule formation, inhibiting their assembly and, hence, are antimitotic agents

• analogues containing functional groups that would allow the conjugation of a homing device were developed [41][42][43][44][45][46]. Some of these functionalized analogues have been recently used for the preparation of antibody–drug conjugates (ADCs) and peptide–drug conjugates (PDCs) [46][47][48][49][50][51

• conjugation of the novel cryptophycin analogues across an appropriate linker to an antibody or peptide. Either a virtually uncleavable triazole (introduced by CuAAC) or scissile ester, carbonate, or carbamate moieties were taken into account. The synthesis of the modified unit B (Scheme 1) started with the

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

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

• worth noting that FPID can be readily regenerated after the peptide coupling reaction. Keywords: cyclic peptide; FPID; hypervalent iodine(III) reagent; recyclable; solid-phase peptide synthesis (SPPS); Introduction The amide bond is one of the most fundamental functional groups in organic chemistry

• reagents, it is still far from ideal because large amounts of chemical wastes are produced during the amide bond formation reaction using these reagents and the coupling reagents cannot be regenerated [10]. Thus, methods for the peptide synthesis which are efficient and atom-economic are still needed

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Pázmány P. stny. 1/A, H-1117 Budapest, Hungary 10.3762/bjoc.14.80 Abstract Cancer is the second leading cause of death affecting nearly one in two people, and the appearance of new cases is projected to rise by

• >70% by 2030. To effectively combat the menace of cancer, a variety of strategies have been exploited. Among them, the development of peptide–drug conjugates (PDCs) is considered as an inextricable part of this armamentarium and is continuously explored as a viable approach to target malignant tumors

• . The general architecture of PDCs consists of three building blocks: the tumor-homing peptide, the cytotoxic agent and the biodegradable connecting linker. The aim of the current review is to provide a spherical perspective on the basic principles governing PDCs, as also the methodology to construct

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• Andrea Angelo Pierluigi Tripodi Szilard Toth Kata Nora Enyedi Gitta Schlosser Gergely Szakacs Gabor Mezo Eötvös Loránd University, Faculty of Science, Institute of Chemistry, Pázmány P. stny. 1/A, H-1117 Budapest, Hungary MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences

• CD13+ HT-1080 human fibrosarcoma and CD13− but integrin positive HT-29 human colon adenocarcinoma cells. However, it seems that the free ε-amino group of Lys in the cycle is not necessary for the biological activity. Therefore, we developed novel cyclic NGR peptide–daunomycin conjugates in which Lys

• ratio of 3:1 after hydrolysis [5][6][7][8][9][10][11]. IsoDGR peptides are bound to RGD-integrin receptors with high affinity [12][13][14]. Due to their function in tumor proliferation, metastasis and angiogenesis, integrin receptors are also promising targets for cancer therapy. Thus, NGR-peptide

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• Sabine Schuster Beata Biri-Kovacs Balint Szeder Viktor Farkas Laszlo Buday Zsuzsanna Szabo Gabor Halmos Gabor Mezo MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, 1117 Budapest, Hungary Institute of Chemistry, Eötvös L. University, 1117 Budapest

• chemotherapeutics. A promising treatment option to overcome these drawbacks can be targeted tumor therapy. This approach is based on the fact that receptors for many regulatory ligands such as peptide hormones are overexpressed on the surface of various cancer cells including gonadotropin-releasing hormone

• incorporated in position 4 and Fmoc-Lys(Mtt)-OH in position 8. After peptide chain elongation the Dde group was removed and 4Lys was butyrylated by using butyric anhydride. Afterwards, the Mtt group was cleaved under mild acidic conditions, followed by Boc-Aoa-OH coupling. After cleavage from the resin with an

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• (X = I or Br) in water [100]. Other examples of water-soluble dendrimers are peptide- and glycol-based dendrimers [102][103]. As a result of their compositional versatility, they have been reported in many applications for biomedical engineering (e.g., glycopeptide dendrimers for drug delivery [104

• ]). The ability of peptide dendrimers to perform catalysis in an aqueous environment has also been investigated [105]. Many different libraries of peptide dendrimers have been used for biocatalytic applications, such as hydrolysis and aldolase reactions [105][106][107][108], showing their potential in

• green catalysis. Peptide dendrimers including aspartate, histidine and serine were utilized by Reymond et al. as catalytic esterase triad. Using fluorogenic 8-acyloxypyrene-1,3,6-trisulfonates as substrate (Figure 7) at the pH optimum of 5.5, triads’ activity was successfully demonstrated [107]. A

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• withdrawal, etc. [26][27][28][29][30][31][32][33][34]. In addition, these azaheterocycles also exhibit anti-inflammatory, antitumor, antiparasitic and anxiolytic activities [35][36][37][38][39][40][41][42]. In particular, 1,4-benzodiazepine derivatives are proposed to serve as a structural mimic of peptide β

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• ]. 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

• acids alone. Further, the rate of formation of peptido RNA depends on the structure of the amino acid, and, to a lesser degree, on that of the ribonucleotide [66], so that a very primitive, not yet encoded form of RNA-induced peptide synthesis can occur under conditions that support the formation and

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• , indicating that the central cyclic peptide core probably has an expanded ring conformation. Garcia-Hartjes et al. synthesised and evaluated the GM1os linked calix[5]arene molecule 31 as shown in Figure 12, and found that compound 31 displayed 100,000 times more potency as compared to GM1os derivatives having

• to come. a) Ribbon and b) surface depictions of the cholera toxin: A11 domain in light blue; A12 domain in dark blue; A13 domain in purple; cystine disulfide in orange; A2 peptide in green and B-subunit in red. Figure prepared using the PyMOL programme from Protein Data Bank file 1XTC.pdb. a

• ) Structure of the cholera toxin showing the location of its carbohydrate binding sites and the structures of the Lewis-y and Ganglioside GM1 ligands; A-subunit (blue), B-subunit (red) and the A2 peptide linker (green). b) Bottom face of the toxin showing the symmetry of the B-subunit and the A2 peptide

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• conjugate with a disulfide linker is favorable to improve the suppression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase mRNA in oligodendrocytes in vivo. This result may be attributable to increased bioavailability of siRNA in the cytoplasm. Similarly, regarding the intracellular delivery of naked peptide

• 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

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• tolerant of other functional groups in the oligosaccharide, for example sialic acids [44] and phosphates [45][46] are completely unaffected; the former is perhaps rather surprising since DMC was first developed as a carboxylic acid activating agent for peptide synthesis by Ishikawa [47]! One caveat to the

• contains a glycopeptide, often termed sialylglycopeptide (SGP), which is comprised of a short peptide linked to a complex biantennary N-glycan. Thus egg yolks can serve as a source of this complex biantennary N-glycan [(NeuAcGalGlcNAcMan)2ManGlcNAc2], following isolation of SGP, and subsequent enzymatic

• oxazoline in a more efficient manner [93]. In related work, Kajihara has recently developed [94] methods that allow selective modification of the complex biantennary N-glycan available from egg yolks. For example, after the peptide is degraded to a single Asn residue by protease digestion (Actinase E), the

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• α-amanitin activity on the targeted cells. An alternative approach to the antibody targeted therapy is represented by small molecule–drug conjugates (SMDCs), where the small molecule – usually a peptide or peptidomimetic receptor ligand – avoids the drawbacks of ADCs such as high manufacturing costs

• and co-workers conjugated α-amanitin to pHLIP (pH low insertion peptide) via linkers of different hydrophobicities [7]. The results indicated that pHLIP could deliver α-amanitin into cells and induce cell death in 48 h by a pH-mediated direct translocation across the membrane and cleavage of the

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• attention has been paid to the recognition element. Peptide nucleic acids (PNA) are DNA mimics with several favorable properties making them a potential alternative to natural nucleic acids for the development of fluorogenic probes, including their very strong and specific recognition and excellent chemical

• make them worthwhile alternatives to the traditionally used oligodeoxynucleotide probes. In this respect, peptide nucleic acids (PNA) [5] have been one of the most widely used alternative oligonucleotide probes in addition to locked and morpholino nucleic acids [6][7]. Although many review articles on

• developments in the areas of fluorogenic PNA probes. Some examples of PNA probes for nucleic acid hybridization and detection that may not be strictly fluorogenic by definition have been included where deemed suitable. Overview of PNA and fluorescent PNA probes Peptide nucleic acids (PNA) are a unique class of