DNA‐Controlled Bivalent Presentation of Ligands for the Estrogen Receptor

Abendroth, Frank; Bujotzek, Alexander; Shan, Min; Haag, Rainer; Weber, Marcus; Seitz, Oliver

doi:10.1002/anie.201101655

Cited by 66 publications

(68 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using longer PEG segments not only raised the probability of the ligand and receptor binding, but also greatly increased the entropic cost through molecular conformations of the tethered chains. Usually models like the worm-like 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 A prominent example of an approach to design bivalent ligands with variable spacer length was reported by Abendrot 103 . In this study, a DNA segment was used as a spacer to precisely control the distance between the ligands matching the estrogen receptor.…”

Section: Ligand Densitymentioning

confidence: 98%

Pathogen Inhibition by Multivalent Ligand Architectures

2016

Self Cite

View full text Add to dashboard Cite

Interfacial multivalent interactions at pathogen-cell interfaces can be competitively inhibited by multivalent scaffolds that prevent pathogen adhesion to the cells during the initial stages of infection. The lack of understanding of complex biological systems makes the design of an efficient multivalent inhibitor a toilsome task. Therefore, we have highlighted the main issues and concerns associated with blocking pathogen at interfaces, which are dependent on the nature and properties of both multivalent inhibitors and pathogens, such as viruses and bacteria. The challenges associated with different cores or carrier scaffolds of multivalent inhibitors are concisely discussed with selected examples.

show abstract

Section: Ligand Densitymentioning

confidence: 98%

Pathogen Inhibition by Multivalent Ligand Architectures

2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Building block 3, 2'-deoxy-5'-O-(4,4'-dimethoxytrityl)-5-(hepta-1,6-diyn- 1-yl)uridine, was synthesized following the reported protocol. 41,42 The azide derived neomycin (4) was synthesized as we have previously described. 39 Trifluoroacetyl protections (4) were required to avoid undesired Cu(II) complexation of the neomycin moiety upon the click conjugation.…”

Section: Synthesis Of the Building Blocks (1-4)mentioning

confidence: 99%

Synthesis of C-5, C-2′ and C-4′-neomycin-conjugated triplex forming oligonucleotides and their affinity to DNA-duplexes

Tähtinen¹,

Granqvist²,

Virta³

2015

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

“…This matrix generates P, i.e, P = exp(τQ), where exp(·) denotes the matrix-exponential. [33]. Right: In multivalent ligand-receptor complexes there exist molecular micro-states which are neither completely bound nor completely unbound.…”

Section: Rebinding Effectsmentioning

confidence: 99%

Implications of PCCA+ in Molecular Simulation

Weber

2018

Computation

Self Cite

View full text Add to dashboard Cite

Upon ligand binding or during chemical reactions the state of a molecular system changes in time. Usually we consider a finite set of (macro-) states of the system (e.g., 'bound' vs. 'unbound'), although the process itself takes place in a continuous space. In this context, the formula χ = XA connects the micro-dynamics of the molecular system to its macro-dynamics. χ can be understood as a clustering of micro-states of a molecular system into a few macro-states. X is a basis of an invariant subspace of a transfer operator describing the micro-dynamics of the system. The formula claims that there is an unknown linear relation A between these two objects. With the aid of this formula we can understand rebinding effects, the electron flux in pericyclic reactions, and systematic changes of binding rates in kinetic ITC experiments. We can also analyze sequential spectroscopy experiments and rare event systems more easily. This article provides an explanation of the formula and an overview of some of its consequences.Keywords: Robust Perron Cluster Analysis; membership function; invariant subspace. MSC: 60J22 The Foundation of PCCA+Molecular simulation is used as a tool to estimate thermodynamical properties. Moreover, it could be used for investigation of molecular processes and their time scales. In computational drug design, e.g., binding affinities of ligand-receptor systems are estimated. In this case, trajectories in a 3N-dimensional space Ω of molecular conformations (N is the number of atoms) are generated. They will be denoted as micro-states x ∈ Ω in the following. After simulation the micro-states are classified as "bound" or "unbound". This classification can be achieved by projecting the state space Ω onto a low number n of macro-states of the system. Spectral clustering algorithms are one possible method in this context. Robust Perron Cluster Analysis (PCCA+) turned out to be a commonly used practical tool for this algorithmic step [1].Conformation Dynamics has been established in the late 1990s. From molecular simulations [2] transition matrices P ∈ R m×m were derived. The entries of P represent conditional transition probabilities between pre-defined m subsets of the state space Ω of a molecular process. Today P would be denoted as Markov State Model. According to the transfer operator theory and PCCA [3] the eigenvectors of these matrices were studied in the early 2000s leading to an empirical observation [4] and Figure 1: Given a matrix X ∈ R m×n of the n m leading eigenvectors of the m × m-transition matrix P, the m rows of X -plotted as n-dimensional points -seem to always form an (n − 1)-simplex. Some of those m points are located at the vertices of the simplices, other points are located on the edges. The points which are located at the n vertices of these simplices represent the thermodynamically stable conformations of the molecular systems. Whereas, the points which are located on the edges of the simplices represent transition regions. In order to transform the (n − 1)-simplex σ 1 ...

show abstract

DNA‐Controlled Bivalent Presentation of Ligands for the Estrogen Receptor

Cited by 66 publications

References 49 publications

Pathogen Inhibition by Multivalent Ligand Architectures

Pathogen Inhibition by Multivalent Ligand Architectures

Synthesis of C-5, C-2′ and C-4′-neomycin-conjugated triplex forming oligonucleotides and their affinity to DNA-duplexes

Implications of PCCA+ in Molecular Simulation

Contact Info

Product

Resources

About