Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• recognition; peptide-based; Introduction Molecular recognition involving amino acids or peptides are important factors in biochemical and medicinal processes [1][2][3]. Amino acids work as biosynthetic building blocks or as signaling molecules. For example, the well-known neurotransmitters glutamate and γ

• a bound glutamate molecule [4]. Peptides often work as signaling molecules or hormones, such as small neuropetide endorphins, produced by the central nervous system to relieve stress or enhance pleasure. They produce signaling cascades in the brain by interacting with opiate receptors. Sometimes

• antibiotic, is used for the treatment of resistant bacterial infections. Its interaction with a small peptidic segment of the bacteria cell wall is a classic example of molecular recognition [6][7]. Peptides are often substrates for protease enzymes [8][9]. Enzymologists have studied the chemical principles

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• , Universitätsstrasse 7, 45141 Essen, Germany 10.3762/bjoc.16.240 Abstract Ultraviolet resonance Raman (UVRR) spectroscopy is a powerful vibrational spectroscopic technique for the label-free monitoring of molecular recognition of peptides or proteins with supramolecular ligands such as guanidiniocarbonyl pyrroles

• UVRR approach from peptides to proteins as binding partners for GCPs is the UV-excited autofluorescence from aromatic amino acids observed for laser excitation wavelengths >260 nm. These excitation wavelengths are in the electronic resonance with the GCP for achieving both a signal enhancement and the

• the results from density functional theory (DFT) calculations. Keywords: GCI; GCP; guanidiniocarbonyl indole; guanidiniocarbonyl pyrrole; UVRR; Raman spectroscopy; resonance Raman; Introduction Supramolecular ligands are capable to selectively bind to peptides and proteins via reversible non

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• cytosine (C) [2]. Similarly, proteins, like microtubules and actin filaments, are self-sorted on the molecular level in living cells [3]. Furthermore, the smaller molecules of life such as sugars [4], peptides, and fatty acids [5] undergo self-sorting in the construction of a cell [6][7]. The above

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• siderophores and modified peptides, are known from Kocuria and Micrococcus [19][20]. In our continuing investigation on secondary metabolites from marine bacteria, five alkanoylimidazoles were obtained from the culture extract of a Kocuria strain isolated from a stony coral. Alkanoylimidazoles are a new and

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• Dongsik Yang Hongjian He Bing Xu Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA 10.3762/bjoc.16.221 Abstract Here, we report the use of an enzymatic reaction to cleave the branch off branched peptides for inducing the morphological transition of the

• assemblies of the peptides. The attachment of DEDDDLLI sequences to the ε-amine of the lysine residue of a tetrapeptide produces branched peptides that form micelles. Upon the proteolytic cleavage of the branch, catalyzed by proteinase K, the micelles turn into nanofibers. We also found that the acetylation

• of the N-terminal of the branch increased the stability of the branched peptides. Moreover, these branched peptides facilitate the delivery of the proteins into cells. This work contributes insights for the development of peptide supramolecular assemblies via enzymatic noncovalent synthesis in

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• described for analytes ranging from inorganic ions over low-molecular-weight neutral and charged organic compounds, such as carboxylic acids, amino acids, and nucleotides, to larger biomolecules such as peptides and proteins [1][2][3][4][5][6][13]. All of these systems have specific areas of application

• , which should give rise to optical probes for dicarboxylates or peptides [46][47][48]. Schematic illustration of the analyte-induced crosslinking of gold nanoparticles containing a mixture of ligands of which one contains a peripheral zinc(II)–dipicolylamine unit while the other one mainly serves to

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• peptide conformations near the glycosylation site and at distant sites [23]. In glycopeptide enkephalin analogs, the only observed conformational effects due to O-glycosylation were on the residue of attachment and its neighboring residue [24]. While for prion peptides, the O-glycosylation (α-GalNAc) is

• -structure relative to the random coil and the effects of the glycosylation were hypothesized to relate to the conformational properties of the peptides in solution (as opposed to their equilibrium structures in solution) [25]. A comprehensive structural study of the O-glycosylation-induced changes in a

• equilibrium of the peptide backbone near the glycosylated residue for a 15-residue mucin peptide. The APDTRP fragment resembled an S-shaped bend and a clustering of low-energy conformations revealed structural similarities between glycosylated and nonglycosylated peptides [23]. The work by Movahedin et al

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• at simple 1D proton spectra to study ligand binding to single amino acids or small peptides to introduce the basic principles and also briefly discuss ligand-detected NMR screening methods. Review One-dimensional 1H NMR spectra and basic principles to study ligand binding by NMR Simple one

• signals from the binding partner. Therefore, this approach is only suitable to study binding of hosts to small guest molecules like amino acids and short peptides. Both a shifting of the signals (chemical shift perturbation) and line broadening are indicative of binding. The chemical shift perturbation is

• supramolecular tweezers that bind to lysine or arginine, tweezers have been titrated to the free amino acids or short peptides, monitoring the Lys and Arg resonances [5][80]. While all resonances of the guest amino acid shift upon tweezer binding, the effect is most severe for the H atoms at the end of the side

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• range of biomolecules: amino acids [8], peptides [9], glycosides [10], nucleosides/nucleotides [11], and lipids [12]. Also, protein-based nano-bio-conjugates [13] have been prepared by ball milling, retaining the native properties of the proteins after mechanochemical synthesis. Boronic acids and their

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• report [207], Lectka and co-workers achieved selective monofluorination of the benzylic C–H bonds of phenylalanine- and tyrosine-like residues in peptides under visible-light photosensitization. After screening a variety of sensitizers, such as 1,2,4,5-tetracyanobenzene, AQN, 1,4-dicyanobenzene, 1

• was achieved with exclusive regioselectivity in peptides, with modest to moderate diastereomeric ratios of the fluorinated products (Scheme 29). With the optimum PSCat in hand, it was necessary to find a protecting group (PG) for the amine that would not undergo fluorination or oxidation when treated

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• ]. Our analysis revealed differences in occupancy and glycan compositions of several proteins as potential HCC tumor biomarkers. Results and Discussion GlypNirO Byonic is powerful software that allows identification of glycopeptides and peptides from complex glyco/proteomic LC–MS/MS datasets but does not

• depleted of six abundant proteins from liver cancer (hepatocellular carcinoma (HCC)) patients and healthy controls. We identified glycopeptides and peptides in the datafiles from these samples using Byonic, searching separately for O- and N-glycopeptides (Supporting Information File 1, Tables S1–S24), and

• we analysed measured enriched glycopeptides, it is likely that unglycosylated peptides forms are underrepresented. We could identify both changes in peptide-specific O-glycan compositions and in O-glycan occupancy. HCC patients had increased glycan occupancy and decreased abundance of monosialylated

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• ; Introduction The interplay of non-covalent interactions between nucleic acids and proteins or peptides is the basis of life and is also often used for the design of artificial small molecules, aiming for sensing or control of biorelevant processes. Many naturally occurring bioactive molecules contain a short

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• implications for the development of a wide range of functional materials [2][3][4][5][6][7][8]. Peptides are arguably the most eminent candidates among all types of biological self-assembling building blocks because of a number of key properties. This includes a high biocompatibility [9][10][11][12][13][14

• -responsiveness of self-assembled peptides has been extensively exploited for potential applications, with particular focus on drug delivery systems (DDS) [40], as injectable gels for tissue engineering [41][42], and biosensing applications [43]. pH-responsive DDS can deliver the drug to a specific tissue or

• organ and protect the payload during the passage through physiological barriers. Most importantly, pH-sensitive DDS are considered as suitable carriers for chemotherapeutics [44][45][46]. Furthermore, peptides also play an important role as active moieties for many diseases, including cancer [47

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• chemistry tools to deliver into living cells has seen a shift of attention from counterion-mediated uptake of cell-penetrating peptides (CPPs) and their mimics, particularly the Schmuck cation, toward thiol-mediated uptake with cell-penetrating poly(disulfide)s (CPDs) and cyclic oligochalcogenides (COCs

• results can be obtained from dose–response curves of the targeted delivery to selected cells and the cytotoxicity in the same experiment, even with poorly optimized cellular systems. Keywords: automation; cell-penetrating peptides; cellular uptake; cytosolic delivery; cytotoxicity; high-content imaging

• challenge is most pronounced with large substrates, such as proteins, oligonucleotides, or nanoparticles, due to the permeability barriers formed by the lipophilic core of the cell membrane [18][19]. In recent decades, the use of arginine-rich cell-penetrating peptides (CPPs) as carriers has emerged as an

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• William A. Donaldson Department of Chemistry, Marquette University, P. O. Box 1881, Milwaukee, WI 53201-1881, USA 10.3762/bjoc.16.166 Abstract The spliceostatins/thailanstatins are a family of linear peptides/polyketides that inhibit pre-mRNA splicing, and as such act as potent cytotoxic

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• Vladimir Kubyshkin University of Manitoba, Dysart Rd. 144, Winnipeg, R3T 2N2, Canada 10.3762/bjoc.16.151 Abstract Fluorine-containing analogues of proline are valuable tools in engineering and NMR spectroscopic studies of peptides and proteins. Their use relies on the fundamental understanding of

• [49][50]. The presence of a fluorine-rich group in the structure is also beneficial for the NMR studies based on the detection of the 19F nucleus [51][52][53]. Limited attention has been given to the polarity effects in the proline analogues though. Few studies reported peptides containing proline

• complex structures: peptides and proteins. Results and Discussion Model compounds The study was originally set up following an assumption that a peptide containing a proline analogue would form a system of three dipoles. The peptide bond itself creates a strong dipole, with a direction that roughly aligns

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• Florian Klepel Bart Jan Ravoo Organic Chemistry Institute and Center for Soft Nanoscience, Westfälische Wilhelms-Universität Münster, Correnstraße 40, 48149 Münster, Germany 10.3762/bjoc.16.131 Abstract Small peptides are involved in countless biological processes. Hence selective binding motifs

• for peptides can be powerful tools for labeling or inhibition. Finding those binding motifs, especially in water which competes for intermolecular H-bonds, poses an enormous challenge. A dynamic combinatorial library can be a powerful method to overcome this issue. We previously reported artificial

• receptors emerging form a dynamic combinatorial library of peptide building blocks. In this study we aimed to broaden this scope towards recognition of small peptides. Employing CXC peptide building blocks, we found that cyclic dimers of oxidized CFC bind to the aromatic peptides FF and YY (K ≈ 229–702 M−1

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• DSM 45348, using the AntiSMASH database [17], and identified in total 14 biosynthetic gene clusters for polyketides and non-ribosomal peptides. Intrigued by this, a strain available from the NBRC culture collections [18] was cultured and examined by HPLC–DAD analysis, which gave several peaks in the

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• Laila F. Awad Mohammed Salah Ayoup Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 426, Alexandria, 21321, Egypt 10.3762/bjoc.16.91 Abstract Recent advances in the chemistry of peptides containing fluorinated phenylalanines (Phe) represents a hot topic in drug research

• the properties of peptides and proteins [5][6][7], influencing aspects such as protein folding, protein–protein interactions, ribosomal translation, lipophilicity, acidity/basicity, optimal pH, stability, thermal stability, and therapeutic properties [8][9][10]. This extends to metabolic properties of

• and activity of peptides in therapeutic vaccines and enzymes has been studied [19][26][27][28][29][30][31][32][33]. In this review we provide an overview for the various syntheses of FPhes and analogues. Five different categories of FPhe are represented and are classified I–V according to the position

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• caused by other compound(s) as both strains have the potential to produce further bioactive SMs, such as cabanillasin, PAX peptides, or rhabdopeptides [26][44][45][46], which will be studied in the future. Furthermore, the identification of fabclavine derivatives described here might support recent

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• comparison with naturally occurring amino acids [14]. Thus, there is still a great effort in finding new potential drugs derived from glycopeptides [4][15]. By using preparative mass spectrometry (pMS) combined with STM on submolecular-resolution peptides and carbohydrates can be investigated regarding their

• investigation of the self assembly of such glycopeptides on metal surfaces will be performed via pMS and STM in further studies. Description of the starting materials 1a–f and 2a–f. Peptide coupling reactions, including the previous Fmoc cleavage. Cleavage of the fully protected peptides 6 and 7. Yields of the

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• peptides or polynucleotides, are also important to encompass. However, capture into structured records is more challenging for these larger therapeutic modalities than for small-molecules that can be merged on the basis of chemistry rules. Notwithstanding, space limitations mean that non-small molecule

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• glycine-containing peptides using an in situ-formed heteroleptic copper complex, [Cu(I)(dmp)(xantphos)]PF6 (Scheme 25) [40]. Under blue light irradiation, glycine esters were readily alkylated using NHP esters in the presence of DABCO as a base. A large panel of NHP esters was introduced to ethyl N

Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides

• Sabrina Müller,
• Jannik Paulus,
• Jochen Mattay,
• Heiko Ihmels,
• Veronica I. Dodero and
• Norbert Sewald

Beilstein J. Org. Chem. 2020, 16, 60–70, doi:10.3762/bjoc.16.8

• peptides or small molecules, thereby controlling geometry and functionality. E-to-Z photoisomerization usually is achieved upon irradiation at 350 nm (π–π* transition), while the Z-to-E isomerization proceeds photochemically upon irradiation at >400 nm (n–π* transition) or thermally. Photoswitchable

• substance, once located at the DNA target, with an external stimulus. Azobenzenes are photoswitchable molecules capable of generating significant structural changes in peptides or small molecules, thereby controlling their geometry and functionality upon irradiation [10][11][12][13]. While isomerization of

• pyrrole and imidazole carboxamides with higher binding affinities than the pyrrole analogs alone [33][34]. We selected 3-(3-(aminomethyl)phenyl)azophenylacetic acid as the linker between both polyamide strands because it was shown to induce hairpins in peptides upon E-to-Z photoisomerization [35][36

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• embryotoxicity of dithienylethene-modified peptides upon photoswitching, using 19 analogues based on the β-hairpin scaffold of the natural membranolytic peptide gramicidin S. We established an in vivo assay in two variations (with ex vivo and in situ photoisomerization), using larvae of the model organism Danio

• rerio, and determined the toxicities of the peptides in terms of 50% lethal doses (LD50). This study allowed us to: (i) demonstrate the feasibility of evaluating peptide toxicity with D. rerio larvae at 3–4 days post fertilization, (ii) determine the phototherapeutic safety windows for all peptides

• , (iii) demonstrate photoswitching of the whole-body toxicity for the dithienylethene-modified peptides in vivo, (iv) re-analyze previous structure–toxicity relationship data, and (v) select promising candidates for potential clinical development. Keywords: diarylethene photoswitch; gramicidin S