Positional Scanning Synthesis of a Peptoid Library Yields New Inducers of Apoptosis that Target Karyopherins and Tubulin

Abstract

We describe the synthesis of a library of 11, 638 N-alkylglycine peptoid trimers in a positional scanning format with adjustment of reaction conditions to account for different reactivities of the monomer building blocks. Evaluation of the library by high-content phenotypic screening for modulators of the cytoskeleton and mitosis resulted in the identification of two apoptosis-inducing peptoids, which, despite their structural similarity, target different proteins and cellular mechanisms. Whereas one peptoid binds to karyopherins, which mediate nuclear transport, the other N-alkylglycine trimer binds tubulin at the vinca alkaloid binding site.

Antiamyloidogenic Activity of Aβ42-Binding Peptoid in Modulating Amyloid Oligomerization

“…A six‐mer peptoid library was constructed and synthesized following the standard split‐and‐pool method . The general structure of the peptoid consists of an inconstant part at the N‐terminal containing four randomized monomers derived from amines commonly used as peptoid building blocks and a constant part at the C‐terminal containing two 1,4‐diaminobutane (Nlys) monomers and a cysteine residue. The hydrophilic Nlys monomers were used to increase the solubility of the peptoid, while the cysteine residue was used to enable the covalent attachment of the peptoids to the gold‐coated SPRi chip (Figure S1a, Supporting Information).…”

“…Peptoid Library Synthesis : A six‐mer peptoid library with one constant cysteine residue on the C‐terminal was synthesized using the conventional split‐and‐pool method . Briefly, the syntheses were conducted with Rink amide resin (capacity: 0.30 mmol g −1 ) and the first two constant Nlys monomers and the four variable monomers were created following the solid‐phase submonomer method .…”

Hypertonicity‐induced cation channels in HepG2 cells: architecture and role in proliferation vs. apoptosis

“…For protein identification, tryptic peptides were separated and analysed by nano‐HPLC–tandem mass spectrometry (MS/MS) (Vendrell‐Navarro et al . ) using an UltiMate TM 3000 RSLCnano system and a Q Exactive™ Hybrid Quadrupole‐Orbitrap mass spectrometer equipped with a nano‐spray flex ion source (Thermo Fisher Scientific). All solvents were of LC‐MS grade.…”

Bio-instructive materials on-demand – combinatorial chemistry of peptoids, foldamers, and beyond

“…The parts in which the peptoids differ are highlighted in blue. 236 In the last decade, the interaction of peptoids with various biological macromolecules has been investigated. Besides the interaction with protein targets, interactions with other classes of macromolecules such as the ribonucleic acids with a high biological impact gain increasing interest.…”