Efficient Screening of Combinatorial Peptide Libraries by Spatially Ordered Beads Immobilized on Conventional Glass Slides.

Screening of one-bead-one-compound (OBOC) libraries is a proven procedure for the identification of protein-binding ligands. The demand for binders with high affinity and specificity towards various targets has surged in the biomedical and pharmaceutical field in recent years. The traditional peptide screening involves tedious steps such as affinity selection, bead picking, sequencing, and characterization.

Digging into the Sequential Space of Thiolactone Precision Polymers: A Combinatorial Strategy to Identify Functional Domains.

Functional sequences of precision polymers based on thiolactone/Michael chemistry are identified from a large one-bead one-compound library. Single-bead readout by MALDI-TOF MS/MS identifies sequences that host m-THPC that is a second generation photo-sensitizer drug. The corresponding Tla/Michael-PEG conjugates make m-THPC available in solution and drug payload as well as drug release kinetics can be fine-tuned by the precision segment.

Specific Decoration of a Discrete Bismuth Oxido Cluster by Selected Peptides towards the Design of Metal Tags.

Metal tags find application in a multitude of biomedical systems and the combination with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) offers an opportunity for multiplexing. To lay the foundation for an increase of the signal intensities in such processes, we herein present a general approach for efficient functionalization of a well-defined metal oxido cluster [Bi O (OH) (SO CF ) (CH CN) ]⋅2 CH CN (1), which can be realized by selecting 7mer peptide sequences via combinatorial means from large one-bead one-compound peptide libraries. Selective cluster-binding peptide sequences (CBS) for 1 were discriminated from non-binders by treatment with H S gas to form the reduction product Bi S , clearly visible to the naked eye.

Polymerizing Like Mussels Do: Toward Synthetic Mussel Foot Proteins and Resistant Glues.

A novel strategy to generate adhesive protein analogues by enzyme-induced polymerization of peptides is reported. Peptide polymerization relies on tyrosinase oxidation of tyrosine residues to Dopaquinones, which rapidly form cysteinyldopa-moieties with free thiols from cysteine residues, thereby linking unimers and generating adhesive polymers. The resulting artificial protein analogues show strong adsorption to different surfaces, even resisting hypersaline conditions.

On the way to precision formulation additives: 2D-screening to select solubilizers with tailored host and release capabilities.

A 2-dimensional high-throughput screening method is presented to select peptide sequences from large peptide libraries for precision formulation additives, having a high capacity to specifically host a drug of interest and provide tailored drug release properties. The identified sequences are conjugated with poly(ethylene glycol) (PEG) to obtain peptide-PEG conjugates that proved to be valuable as solubilizers for small organic molecule drugs to overcome limitations of poor water-solubility and low bio-availability. The 2D-screening method selects peptide sequences on both (i) high loading capacities and (ii) preferred drug-release capabilities as demonstrated on an experimental Tau-protein aggregation inhibitor/Tau- deaggregator with potentials for an anti-Alzheimer disease drug (BB17).