Antimicrobial peptides (AMPs) are critical components of the innate immune system and exhibit bactericidal activity against a broad spectrum of bacteria. We investigated the use of N-substituted glycine peptoid oligomers as AMP mimics with potent antimicrobial activity. The antimicrobial mechanism of action varies among different AMPs, but many of these peptides can penetrate bacterial cell […]

Measuring the synthesis of new proteins in the context of a much greater number of pre-existing proteins can be difficult. To overcome this obstacle, bioorthogonal noncanonical amino acid tagging (BONCAT) can be combined with stable isotope labeling by amino acid in cell culture (SILAC) for comparative proteomic analysis of de novo protein synthesis (BONLAC). In […]

N-Substituted glycine peptoid oligomers have recently attracted attention for their metal binding capabilities. Due to their efficient synthesis on solid phase, peptoids are well suited for generation of compound libraries, followed by screening for molecular recognition and other diverse functional attributes. Ideally, peptoids could be simultaneously screened for binding to a number of metal species. […]

The androgen receptor (AR) is a major therapeutic target in prostate cancer pharmacology. Progression of prostate cancer has been linked to elevated expression of AR in malignant tissue, suggesting that AR plays a central role in prostate cancer cell biology. Potent therapeutic agents can be precisely crafted to specifically target AR, potentially averting systemic toxicities […]

Peptomers are oligomeric molecules composed of both α-amino acids and N-substituted glycine monomers, thus creating a hybrid of peptide and peptoid units. Peptomers have been used in several applications such as antimicrobials, protease inhibitors, and antibody mimics. Despite the considerable promise of peptomers as chemically diverse molecular scaffolds, we know little about their conformational tendencies. […]

Synthetic short interfering RNA (siRNA) oligonucleotides can trigger the RNA interference pathway and lead to selective gene silencing. Despite considerable enthusiasm and investment, formidable challenges remain that may deter translating this breakthrough discovery into clinical applications. In particular, the development of efficient, nontoxic, nonimmunogenic methods for delivering siRNA in vivo has proven to be exceptionally […]

Chemical ligation protocols were explored for generating semisynthetic peptoid–protein hybrid architectures containing a native serine residue at the ligation site. Peptoid oligomers bearing C-terminal salicylaldehyde esters were synthesized and ligated to the N-terminus of the RNase S protein or the therapeutic hormone PTH(1–34) polypeptide. This technique will expand the repertoire of strategies to enable design […]

Peptidomimetics are classes of molecules that mimic structural and functional attributes of polypeptides. Peptidomimetic oligomers can frequently be synthesized using efficient solid phase synthesis procedures similar to peptide synthesis. Conformationally ordered peptidomimetic oligomers are finding broad applications for molecular recognition and for inhibiting protein-protein interactions. One critical limitation is the limited set of design tools […]

We report the first example of chemoselective fragment condensation, through native amide bond formation, between peptoid and peptide oligomers. Peptoid oligomers bearing C-terminal salicylaldehyde esters were synthesized and ligated to peptides containing N-terminal serine or threonine residues. We investigate the ligation efficiency of peptoid oligomers varying in length, sequence, and C-terminal steric bulk. These protocols […]

There is a significant unmet need for new antimicrobial agents that can address antimicrobial resistance. One promising group of antimicrobials is the antimicrobial peptides (AMPs) and their synthetic mimics. In particular, synthetic sequence-specific oligomers of N-substituted glycine, termed “peptoids”, have been found to show potent antimicrobial activity against bacterial pathogens in vitro and can act […]