A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• -linked precursor structure emerging from the dolichol pathway into complex structures. Enzymes involved include mannosidases, glucosidases, some enzymes facilitating protein folding, and also enzymes that direct acid hydrolases to the lysosome. 6) N-glycan branching: These glycogenes are responsible for

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• elucidate three-dimensional structures of proteins. However, the substitution of proline by one of the remaining 19 coded amino acids can be harmful to protein folding and the functional properties. This is usually explained by the absence of the amide hydrogen atom and the cyclic nature of the proline ring

• preferences should be considered when judging the stability of the folded structures containing fluoroprolines. 2.6 Kinetics of the amide rotation The kinetic stability of the amide conformers generates another important aspect of protein folding. Generally, the amide rotation is considered very slow in

• around peptidyl-prolyl [56]. Some other common factors, such as the pH value or the ionic strength, are believed to have a very minor, if any, influence [53]. The enhancement of the amide rotation rate by fluoroprolines can have an effect on the overall protein folding velocity. An impairment of the

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• , protein folding, and potentially small-molecule library screening, as it can broaden the accessibility of quantitative NMR spectroscopy to a wider range of laboratories. Ligand-observed protein binding interactions In addition to protein-observed fluorine (PrOF) NMR spectroscopy, ligand-observed fluorine

• , providing simultaneous access to both structural and dynamic information that would be difficult to obtain using traditional 13C, 1H and 15N,1H-HSQC NMR techniques. Protein folding From the late 1960s and early 1970s 19F NMR has firmly established itself as a highly versatile and powerful analytical tool

• , it is possible to accurately track the complete chain of events that take place within the molecule upon interaction and/or folding. Given that the intermediates involved in protein folding and binding are difficult to observe owing to the short-lived nature of the states and their marginal

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

• -glycosylation; O-glycosylation; Python; Introduction Glycosylation is a key post-translational modification critical for protein folding and function in eukaryotes [1][2][3]. Diverse types of glycosylation are known, all involving modification of specific amino acid residues with complex carbohydrate

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• , implicated in protein folding and structural stability, and mediating interactions with receptors and with the environment. All N-glycans share a common core from which linear or branched arms stem from, with functionalization specific to different species and to the cells’ health and disease state. This

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

• by the solvent (Kbenzene ≈ Kwater > Kdichloromethane). These are, however, still poorly understood and will not be further addressed here (see [74][77][84] for some discussions). It is very well known that a proline-to-fluoroproline substitution alters protein folding. Predominantly, the effect onto

• process, which contributes to the rate-limiting steps in the protein folding [91] and molecular timing phenomena [92]. In peptidyl-prolyl bonds, the transition between the rotational states cis-amide and trans-amide usually occurs in the mHz scale, with the barriers of rotation around 80–90 kJ mol−1 (in

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

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

• 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

Adhesion, forces and the stability of interfaces

• Robin Guttmann,
• Johannes Hoja,
• Christoph Lechner,
• Reinhard J. Maurer and
• Alexander F. Sax

Beilstein J. Org. Chem. 2019, 15, 106–129, doi:10.3762/bjoc.15.12

• introduced by Kauzmann [9] to explain protein folding in analogy with the transfer of a non-polar solute from water into a non-polar solvent. This process was attributed to the poor solubility of the solute in water. Wolfenden and Lewis [10], on the other hand, assumed “that a strong favorable interaction

Dispersion interactions

• Peter R. Schreiner

Beilstein J. Org. Chem. 2018, 14, 3076–3077, doi:10.3762/bjoc.14.286

• but it is certainly attenuated [8]. We are still in the process of understanding just by how much. LD is a driving force for molecular aggregation that plays a key role in the thermodynamic stability, molecular recognition, chemical selectivity through transition-state stabilization, protein folding

Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study

• Ahmet Altun,
• Frank Neese and
• Giovanni Bistoni

Beilstein J. Org. Chem. 2018, 14, 919–929, doi:10.3762/bjoc.14.79

• importance for regulating molecular properties like polarizability [1] and in various biochemical processes, including protein folding [2] and stability [3], replication of DNA and RNA [4], enzyme catalysis [5], proton relay mechanism [6], and drug delivery [7]. Energy decomposition analysis (EDA) schemes

How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution

• Addy Pross and
• Robert Pascal

Beilstein J. Org. Chem. 2017, 13, 665–674, doi:10.3762/bjoc.13.66

• required by the Second Law (Figure 1A). With regard to living organisms, the situation is more complex. On the one hand, association processes directly driven by the Second Law are common in living organisms (e.g., protein folding, the assembly of protein sub-units through molecular recognition, assembly

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• ; peptide phosphorylation; protein folding; Introduction Amyloid fibrils are one of the most important and studied self-assembled materials in nature. A wide range of peptides and proteins with various primary sequences and functions are able to form these wel organized and highly stable aggregates under

• intramolecular Coulombic repulsions between negatively charged glutamate residues and the phosphate, or in electrostatic pairing with positively charged lysine or arginine residues, resulting in the perturbation of higher ordered secondary structures [53]. The impact of electrostatics on peptide and protein

• folding and self-assembly has been studied extensively [12][53], and it is known that the impact of the phosphate group charge strongly depends on the pH and the neighboring residues in the peptide [53][54]. In contrast to the accepted model where negatively charged phosphates must be close to the N

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• concentrations. In another rare genetic disease, the rescue by multimeric correctors of the mutant CFTR protein implied in cystic fibrosis led to the first report of a multivalent effect for amending protein folding defects in cells [26]. As judged by EC50 (half-maximal effective concentration) values, trivalent

• DNJ clusters 2 were indeed up to 225-fold more efficient as CFTR correctors than the clinical candidate N-Bu DNJ (1), a potent inhibitor of trimming ER glucosidases [26]. Taken together, these recent studies provide new therapeutic answers for a number of protein folding disorders [27][28] but also

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• storage disorder [8][9]. In 2013, the first description of a multivalent effect for correcting protein folding defects in cells was reported with trivalent DNJ clusters [10]. These compounds were found to overcome the processing defect of the mutant CFTR protein involved in cystic fibrosis, and to be up

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• are structural motifs commonly found in bioactive peptides, which, besides being fundamental in protein folding, play a central role as molecular-recognition elements [31][32][33][34]. In addition to the most frequently occurring β and γ-turns, reversal of the polypeptide chain direction in globular

A bisazobenzene crosslinker that isomerizes with visible light

• Subhas Samanta,
• Harris I. Qureshi and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2012, 8, 2184–2190, doi:10.3762/bjoc.8.246

• the effects of crosslinkers on protein folding led to the conclusion that photocontrol of folding is best achieved by using rigid crosslinkers that undergo a large change in end-to-end distance upon photoisomerization [6]. Previously, we reported the design and synthesis of the rigid bisazobenzene

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• cell-surface binding events, such as cell growth and differentiation, cell proliferation, cell adhesion, binding of pathogens, fertilization and immune responses [1][2]. Furthermore, glycans assist in intracellular protein folding and transport. Pathogenic processes, such as chronic inflammation, viral

Investigation of the network of preferred interactions in an artificial coiled-coil association using the peptide array technique

• Raheleh Rezaei Araghi,
• Carsten C. Mahrenholz,
• Rudolf Volkmer and
• Beate Koksch

Beilstein J. Org. Chem. 2012, 8, 640–649, doi:10.3762/bjoc.8.71

• . Further, the stability and the stoichiometry of selected sequences were examined by CD and SEC in solution. Results and Discussion Screening system: Coiled coils are a highly populated class of protein-folding motifs that exhibit a distinctive heptad repeat sequence, conventionally labeled with the