The isolation of ligands for large numbers of proteins is an important goal in proteomics. Whereas peptide libraries are rich sources of protein-binding molecules, native peptides have certain undesirable properties, such as sensitivity to proteases that make them less than ideal for some applications. We report here the construction and characterization of large, chemically diverse combinatorial libraries of peptoids (N-substituted oligoglycines). A protocol for the isolation of specific protein-binding molecules from these libraries is described. These data suggest that peptoid libraries will prove to be inexpensive and convenient sources of protein ligands.

Microwave irradiation reduces the reaction time for the solid-phase synthesis of peptoids. Under these conditions, coupling of each residue requires only 1 min. The purity and yields of peptoids synthesized in this way are as good as or better than those achieved using standard methods. [reaction: see text]

Endocrine therapy is the mainstay of treatment in estrogen receptor-positive breast cancers and significantly reduces disease recurrence and breast cancer-related mortality. However, acquired resistance to therapy has been noted in nearly one-third of women treated with tamoxifen and other endocrine therapies. Mutations in the estrogen receptor have long been speculated to play a role in endocrine therapy resistance but have been rarely detected. However, recent studies utilizing next-generation sequencing on estrogen receptor-positive, metastatic clinical samples have revealed that recurrent ESR1 mutations are far more frequent than previously thought and may play an important role in acquired endocrine therapy resistance. Here we review recent advances in detection and characterization of ESR1 mutations in advanced, endocrine therapy-resistant breast cancers.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0494-7) contains supplementary material, which is available to authorized users.

Transcriptional coactivator-binding peptoids were isolated from a large combinatorial library. One of these molecules is shown to function as a potent activation domain surrogate in mammalian cells. Up to a 900-fold increase in expression of a Gal4-responsive reporter gene is observed when a steroid conjugate of the peptoid is incubated with HeLa cells expressing a Gal4 DNA-binding domain (DBD)-glucocorticoid receptor ligand-binding domain (GRLBD) fusion protein.