ONE-BEAD-TWO-COMPOUND MACROCYCLIC LIBRARY AND METHODS OF PREPARATION AND USE
A one-bead-two-compound combinatorial synthesis technique provides libraries of macrocyclic peptidomimetic compounds and compositions with use as ligands for the Ephrin type-A receptor 2 (EphA2). The one-bead-two-compound technique and libraries of macrocyclic compounds are useful as research tools in drug discovery and/or to treat or prevent a range of diseases or disorders.
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Paragraph 0160; 0161; 0169
(2018/11/02)
One-Bead-Two-Compound Thioether Bridged Macrocyclic γ-AApeptide Screening Library against EphA2
Identification of molecular ligands that recognize peptides or proteins is significant but poses a fundamental challenge in chemical biology and biomedical sciences. Development of cyclic peptidomimetic library is scarce, and thus discovery of cyclic peptidomimetic ligands for protein targets is rare. Herein we report the unprecedented one-bead-two-compound (OBTC) combinatorial library based on a novel class of the macrocyclic peptidomimetics γ-AApeptides. In the library, we utilized the coding peptide tags synthesized with Dde-protected α-amino acids, which were orthogonal to solid phase synthesis of γ-AApeptides. Employing the thioether linkage, the desired macrocyclic γ-AApeptides were found to be effective for ligand identification. Screening the library against the receptor tyrosine kinase EphA2 led to the discovery of one lead compound that tightly bound to EphA2 (Kd = 81 nM) and potently antagonized EphA2-mediated signaling. This new approach of macrocyclic peptidomimetic library may lead to a novel platform for biomacromolecular surface recognition and function modulation.
Synthesis and applications of polyamine amino acid residues: Improving the bioactivity of an analgesic neuropeptide, neurotensin
Conjugated polyamines are potential carriers for biothera- peutics targeting the central nervous system. We describe an efficient synthesis of a polyamine-based amino acid, lysine-trimethylene(diNo-syl)-spermine(triBoc) with Dde or Fmoc orthogonal protect
Zhang, Liuyin,Lee, Hee-Kyoung,Pruess, Timothy H.,White, H. Steve,Bulaj, Grzegorz
supporting information; experimental part
p. 1514 - 1517
(2010/02/28)
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