We have synthesized and characterized a family of structured oligo-N-substituted-glycines (peptoids) up to 36 residues in length by using an efficient solid-phase protocol incorporate chemically diverse side chains sequence-specific fashion. investigated polypeptoids containing with chiral center adjacent the main chain nitrogen. Some these sequences stable secondary structure, despite achirality polymer backbone its lack hydrogen bond donors. In both aqueous organic solvents, peptoid...

Polymers of N-substituted glycines (“peptoids”) containing chiral centers at the α position their side chains can form stable structures in solution. We studied a prototypical peptoid, consisting five para -substituted ( S )- N -(1-phenylethyl)glycine residues, by NMR spectroscopy. Multiple configurational isomers were observed, but because extensive signal overlap, only major isomer all cis -amide bonds was examined detail. The data for this molecule, conjunction with previous CD...

Substantial progress has been made in the synthesis and characterization of various oligomeric molecules capable autonomous folding to well-defined, repetitive secondary structures. It is now possible investigate sequence−structure relationships driving forces for these systems. Here, we present detailed analysis by X-ray crystallography, NMR, circular dichroism (CD) helical structures formed N-substituted glycine (or "peptoid") oligomers with α-chiral, aliphatic side chains. The crystal...

Foldamers are an intriguing family of biomimetic oligomers that exhibit a propensity to adopt stable secondary structures. N-Substituted glycine oligomers, or "peptoids", prototypical example these foldamer systems and known form helix resembling polyproline type I. Ongoing studies seek improve the stability peptoid folding discover new structure motifs. Here, we report peptoids undergo highly efficient head-to-tail macrocyclization reactions. A diverse array sequences from pentamers 20mers...

Many naturally occurring biopolymers (i.e., proteins, RNA, DNA) owe their unique properties to well-defined three-dimensional structures. These attributes have inspired the design and synthesis of folded architectures with functions ranging from molecular recognition asymmetric catalysis. Among these are synthetic oligomeric peptide (“foldamer”) mimics, which can display conformational ordering at short chain lengths. Foldamers, however, not been explored as platforms for This report...

A nanoparticle magnetic resonance imaging (MRI) contrast agent was developed by conjugation of more than 500 gadolinium chelate groups onto a viral capsid. The high density paramagnetic centers and slow tumbling rate modified MS2 capsids provided enhanced T1 relaxivities up to 7200 mM-1s-1 per particle. bimodal generated sequential fluorescein Gd3+ chelate. These results illustrate the potential for engineering natural protein assemblies address bionanotechnology applications.

We explore strategies to enhance conformational ordering of N-substituted glycine peptoid oligomers. Peptoids bearing bulky N-alkyl side chains have previously been studied as important examples biomimetic "foldamer" compounds, they exhibit a capacity populate helical structures featuring repeating cis-amide bonds. Substantial cis/trans amide bond isomerization, however, gives rise heterogeneity. Here, we report the use N-aryl tool enforce presence trans-amide bonds, thereby engendering...

Head-to-tail cyclodimerization of resin-bound oligopeptides bearing azide and alkyne groups occurs readily by 1,3-dipolar cycloaddition upon treatment with CuI. The process was found to be independent peptide sequence, sensitive the proximity resin, solvent composition, facile for α- β-peptides but not γ-peptides, inhibited inclusion tertiary amide linkages. Peptides shorter than hexamers were predominantly converted cyclic monomers. Oligoglycine oligo(β-alanine) chains underwent...

Macrocyclic constraints are often employed to rigidify the conformation of flexible oligomeric systems. This approach has recently been used organize structure peptoid oligomers, which peptidomimetics composed chemically diverse N-substituted glycine monomer units. In this review, we describe advances in synthesis and characterization cyclic peptoids. We evaluate how installation covalent between oligomer termini or side chains effective defining conformations. also discuss potential...

Abstract We investigated the antimicrobial activities of N‐substituted glycine “peptoid” oligomers incorporating cationic and hydrophobic side chains. Head‐to‐tail macrocyclization was employed to enhance activity. Both linear cyclic peptoids, ranging from six ten residues, demonstrate potent activity against Gram‐positive Gram‐negative bacteria. These peptoids do not cause significant lysis human erythrocytes, indicating selective Conformational ordering established upon is generally...

Unnatural amino acids with useful chemical functionality can replace phenylalanine in bacterial proteins. Coexpression of a promiscuous phenylalanine-tRNA synthetase mutant enables the synthesis target proteins bearing iodophenyl, cyanophenyl, ethynylphenyl, azidophenyl, and pyridyl groups (see general structures). Proteins incorporating analogues have range potential applications, including Pd-mediated conjugation (R=CCH), photoaffinity labeling (R=N3), X-ray phasing (R=I), novel metal...

A mutant yeast phenylalanine transfer RNA (ytRNAPheAAA) containing a modified (AAA) anticodon was generated to explore the feasibility of breaking degeneracy genetic code in Escherichia coli. By using an E. coli strain co-transformed with ytRNAPheAAA and phenylalanyl-tRNA synthetase, we demonstrate efficient replacement (Phe) by L-3-(2-naphthyl)alanine (Nal) at UUU, but not UUC codons.

We present an analysis of the conformational preferences N-substituted glycine peptoid oligomers. survey backbone conformations observed in experimentally determined structures and provide a comparison with high-level quantum mechanics calculations short The dominant sources structural variation derive from: side-chain dependent cis/trans isomerization amide bonds, side chain stereochemistry, flexibility psi dihedral angle. find good agreement between clustering torsion angles local...

Non-natural polymers with well-defined three-dimensional folds offer considerable potential for engineering novel functions that are outside the scope of biological polymers. Here we describe a family N-substituted glycine or “peptoid” nonamers into an unusual “threaded loop” structure exceptional thermal stability and conformational homogeneity in acetonitrile. The is chain-length-specific relies on bulky, chiral side chains chain-terminating functional groups stability. Notable elements...

Peptoid molecules are biomimetic oligomers that can fold into unique three-dimensional structures. As part of an effort to advance computational design folded oligomers, we present blind-structure predictions for three peptoid sequences using a combination Replica Exchange Molecular Dynamics (REMD) simulation and Quantum Mechanical refinement. We correctly predicted the structure N -aryl trimer within 0.2 Å rmsd-backbone cyclic nonamer accuracy 1.0 rmsd-backbone. X-ray crystallographic...

New chemical inhibitors of protein-protein interactions are needed to propel advances in molecular pharmacology. Peptoids peptidomimetic oligomers with the capability inhibit by mimicking protein secondary structure motifs. Here we report silico design a macrocycle primarily composed peptoid subunits that targets β-catenin:TCF interaction. The interaction plays critical role Wnt signaling pathway which is over-activated multiple cancers, including prostate cancer. Using Rosetta suite...

Glycoproteins adhered on the cellular membrane play a pivotal role in wide range of functions. Their importance is particularly relevant recognition process between infectious pathogens (such as viruses, bacteria, toxins) and their host cells. Multivalent interactions at pathogen-cell interfaces govern binding events can result strong specific interaction. Here we report an approach to mimic cell surface presentation carbohydrate ligands by multivalent display sugars peptoid nanosheets. The...

We describe an efficient protocol to effect multisite conjugation reactions oligomers on solid-phase support. Sequence-specific N-substituted glycine "oligopeptoids" were utilized as substrates for azide−alkyne cycloaddition reactions. Diverse groups, including nucleobases and fluorophores, conjugated at up six positions peptoid side chains with yields ranging from 88 96%. This strategy will be broadly applicable generating polyvalent displays peptides other scaffolds, allowing precise...

N-Substituted glycine peptoid oligomers were used as substrates for azide-alkyne [3 + 2] cycloaddition conjugation reactions and then elaborated through additional rounds of oligomerization cycloaddition. This novel sequential technique allowed the generation complex peptidomimetic products in which multiple heterogeneous pendant groups site-specifically positioned along oligomer scaffold. Studies a water-soluble estradiol–ferrocene conjugate demonstrated potential application modular...

The last sentence of this book review should have read, “This will be an important resource for bioorganic chemists, particularly those who wish to establish that the foldamer field is maturing with great exuberance and promise.” editorial office apologises mistake.

Covalent macrocyclic constraints can be readily installed on N-substituted glycine "peptoid" oligomer substrates. Cu(I)-catalyzed [3+2] cycloaddition reactions were conducted solid support to ligate peptoid side chain azide and alkyne functionalities. Intramolecular macrocycle formation is facilitated by preorganizing the reactive groups across one turn of helical secondary structure. These results confirm that conformational ordering exploited assist macrocyclization folded oligomers.