Synthesis and screening of bead-displayed combinatorial libraries

Doran, Todd M.; Dickson, Paige; Ndungu, John M.; Ge, Pengfei; Suponitsky-Kroyter, Irena; An, Hongchan; Kodadek, Thomas

doi:10.1016/bs.mie.2019.02.005

Cited by 11 publications

(4 citation statements)

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“…[8][9][10][11][12][13] OBOC libraries are screened by incubating the beads with a fluorescently labelled target protein in the presence of a large excess of unlabelled, diverse competitor proteins. [14][15][16] Beads that retain a high level of fluorescence are separated from the bulk of the library and the compound on the bead is characterized by tandem mass spectrometry after release form the bead. 17 This process has been made far more powerful and efficient by applying the DNA-encoding technology developed by Clark and co-workers 18 to the OBOC platform.…”

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confidence: 99%

Structural characterization of a peptoid-inspired conformationally constrained oligomer (PICCO) bound to streptavidin

et al. 2020

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Structural characterization of a peptoid-inspired conformationally constrained oligomer (PICCO) bound to streptavidin

et al. 2020

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“…In addition, the highthroughput "split-and-pool" combinatorial approach allows the synthesis of very large libraries of peptoid sequences simultaneously, such that a single bead contains a single unique sequence. [38][39][40] This synthesis method combined with a functional screen and a mass spectrometry-sequencing method, [41] allows the efficient identification of the "hit" sequence for specific applications. This method has been successfully applied to discover high-affinity peptoid ligands for numerous pharmaceutically relevant receptors [38,40,42,43] .…”

Section: Synthesis Of Sequence-defined Peptoidsmentioning

confidence: 99%

Engineering the atomic structure of sequence-defined peptoid polymers and their assemblies

Xuan

Zuckermann

2020

Polymer

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Peptoids are a family of sequence-defined, non-natural biomimetic polymers which show excellent properties including good chemical and enzymatic stability and high structural tunability. The solid-phase submonomer synthesis method allows precise control over the identity and sequence of chemically diverse side chains, enabling the atomic engineering of their chemical structures for a variety of applications. This unprecedented level of structural control enables access to atomically defined threedimensional chain conformations and assemblies, facilitating the design and optimization of a variety of nanoscale architectures that can function in biology and materials science. In order to approach the rational design of peptoid materials in a more predictive and precise manner, it is crucial to fully understand how chemical information, in the form of the monomer sequence, encodes their folding and assembly into structurally defined, functional 3D shapes. This perspective focuses on recent studies into the atomic engineering of peptoid nanostructures by examining the impact of sequence variations on their secondary and three-dimensional structures, as well as their functional properties.

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“…For SPS, large one bead one compound libraries are synthesized using beads as solid supports with a split and mix reaction path in either syringes [ 11 ] or miniaturized in microtiter plates. [ 12 ] To achieve spatial resolution on an array format, SPOT synthesis was developed by Frank 30 years ago.…”

Section: Introductionmentioning

confidence: 99%

Nanoliter Scale Parallel Liquid–Liquid Extraction for High‐Throughput Purification on a Droplet Microarray

Wiedmann

Demirdögen

Schmidt

et al. 2022

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smll.202204512. approved as a new drug. [2] Only around 50 drugs are approved by the FDA in a year and there is a high demand to continue and improve this trend. Especially thinking about orphan drugs, it is important to reduce the time and cost consumption in all stages of the drug development process. [1] In order to accelerate development of novel functional materials, chemicals, or drug candidates, high-throughput and miniaturized synthetic methods are important. [3] Integration of such miniaturized synthesis with biological high-throughput screenings (chemBIOS approach) [4][5][6] is essential to get rid of the technological and conceptual gap between these two steps in drug discovery. [7] This is necessary to accelerate the hit detection and optimization in the early stage of drug development, which can usually take 6 years or more. [8] Until now, this has been challenging partly due to the necessity of purification of synthesized compounds in highly miniaturized and in parallel high-throughput way. [9] Moreover, the purification methods have to be compatible with the same platform to be used for both synthesis and biological screenings. For this reason, the overwhelming majority of miniaturized highthroughput synthesis methods is still done using solid-phase synthesis (SPS), thus, allowing simple removal of side products and added reagents by washing. [10]

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Synthesis and screening of bead-displayed combinatorial libraries

Cited by 11 publications

References 55 publications

Structural characterization of a peptoid-inspired conformationally constrained oligomer (PICCO) bound to streptavidin

Structural characterization of a peptoid-inspired conformationally constrained oligomer (PICCO) bound to streptavidin

Engineering the atomic structure of sequence-defined peptoid polymers and their assemblies

Nanoliter Scale Parallel Liquid–Liquid Extraction for High‐Throughput Purification on a Droplet Microarray

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