Efficient method for the preparation of peptoids [oligo(N-substituted glycines)] by submonomer solid-phase synthesis

Zuckermann, Ronald N.; Kerr, Janice M.; Kent, Stephen B. H.; Moos, Walter H.

doi:10.1021/ja00052a076

Cited by 1,190 publications

(1,231 citation statements)

References 0 publications

Supporting

Mentioning

1,223

Contrasting

Unclassified

Order By: Relevance

“…Exact peptoid sequences can be designed and synthesized using the submonomer solid-phase method (20). The ability to synthesize an exact polymer sequence enables atomic-level control over molecular design parameters, such as polymer chain length, sequence patterning, and side-chain chemistry.…”

mentioning

confidence: 99%

Assembly and molecular order of two-dimensional peptoid nanosheets through the oil–water interface

Robertson

Olivier

Qian

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

100

View full text Add to dashboard Cite

Significance Peptoid nanosheets are an emerging class of 2D nanomaterials that have the potential for use in a variety of applications ranging from molecular sensors to artificial enzymes. Because peptoids are highly designable polymers, nanosheets provide a general platform on which to display an enormous diversity of functionalities. Nanosheets are known to form through a unique monolayer compression mechanism, catalyzed by the air–water interface. Here we demonstrate that nanosheets can be formed via adsorption of peptoids at an oil–water interface. Using vibrational sum frequency spectroscopy, we show that electrostatic interactions are essential in the formation of an ordered peptoid monolayer at the interface, a critical intermediate in the nanosheet assembly pathway. These findings open the door for enhancing the complexity and functionality of 2D nanomaterials.

show abstract

mentioning

confidence: 99%

Assembly and molecular order of two-dimensional peptoid nanosheets through the oil–water interface

Robertson

Olivier

Qian

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

100

View full text Add to dashboard Cite

show abstract

“…Peptoids were synthesized on an ABI 433A peptide synthesizer or a parallel synthesis robot on Rink amide resin according to the submonomer method (27,54). Briefly, the amide on the nascent chain is bromoacetylated, followed by SN2 displacement of bromide by a primary amine to form the side chain (see SI Text for amines used).…”

Section: Methodsmentioning

confidence: 99%

“…Poly-N-substituted glycines (peptoids) comprise another class of peptidomimetics that differ from peptides only in that peptoid side chains are attached to the backbone amide nitrogen rather than to the ␣-carbon (27), making them protease-resistant (28). More than any of the other peptidomimetic systems under study (29), including ␤-peptides (26,30), ␤-peptoids (31), oligoureas (32), and oligo(phenylene ethynylene)s (33), peptoids (34)(35)(36) are particularly well suited for AMP mimicry because they are easily synthesized on solid phase (by using conventional peptide synthesis equipment) with access to diverse sequences at relatively low cost (27). Any chemical functionality available as a primary amine can be incorporated via a submonomer synthetic method (27); thus, peptoids are highly and finely tunable.…”

mentioning

confidence: 99%

Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides

Chongsiriwatana¹,

Patch²,

Czyzewski³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

573

578

View full text Add to dashboard Cite

Antimicrobial peptides (AMPs) and their mimics are emerging as promising antibiotic agents. We present a library of ''ampetoids'' (antimicrobial peptoid oligomers) with helical structures and biomimetic sequences, several members of which have low-micromolar antimicrobial activities, similar to cationic AMPs like pexiganan. Broad-spectrum activity against six clinically relevant BSL2 pathogens is also shown. This comprehensive structure-activity relationship study, including circular dichroism spectroscopy, minimum inhibitory concentration assays, hemolysis and mammalian cell toxicity studies, and specular x-ray reflectivity measurements shows that the in vitro activities of ampetoids are strikingly similar to those of AMPs themselves, suggesting a strong mechanistic analogy. The ampetoids' antibacterial activity, coupled with their low cytotoxicity against mammalian cells, make them a promising class of antimicrobials for biomedical applications. Peptoids are biostable, with a protease-resistant N-substituted glycine backbone, and their sequences are highly tunable, because an extensive diversity of side chains can be incorporated via facile solid-phase synthesis. Our findings add to the growing evidence that nonnatural foldamers will emerge as an important class of therapeutics.antibiotics ͉ peptidomimetics ͉ structure-activity studies N atural antimicrobial peptides (AMPs) defend a wide array of organisms against bacterial pathogens and show potential as supplements for or replacements of conventional antibiotics, because few bacteria have evolved resistance to them (1-3). Many AMPs kill bacteria by permeabilization of the cytoplasmic membrane, causing depolarization, leakage, and death (4), whereas others target additional anionic bacterial constituents (e.g., DNA, RNA, or cell wall components) (2, 5). Amphipathic secondary structures in which residues are segregated into hydrophobic and cationic regions ( Fig. 1 A and B) are the hallmark of most AMPs (6). Regardless of their final target of killing, AMPs must interact with the bacterial cytoplasmic membrane, and their amphipathicity is integral to such interactions (1, 2, 7). Additionally, their cationic nature imparts AMPs with some measure of selectivity, because mammalian cell membranes are largely zwitterionic. The precise nature of AMP-membrane interactions remains controversial and actively debated; a variety of mechanisms have been proposed, including the carpet (4), barrel-stave pore (4), toroidal pore (8), and aggregate (9) models. Nevertheless, a considerable number of structure-activity investigations have elucidated how the physicochemical properties of these molecules relate to their biological activities (4,7,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).Although AMPs have been actively studied for decades (23-25), they have yet to see widespread clinical use (1). This is due in part to the vulnerability of many peptide therapeutics to rapid in vivo degradation, which dramatically reduces their bioavailability. Nonnatural mimics of AMPs...

show abstract

“…28 Therefore, use of [2,5-dimethylfuran]-protected maleimide building blocks was expected to allow introduction of a maleimide unit into any position of the chain.…”

Section: 27 5'mentioning

confidence: 99%

Protected Maleimide Building Blocks for the Decoration of Peptides, Peptoids, and Peptide Nucleic Acids

et al. 2013

View full text Add to dashboard Cite

Monomers allowing for the introduction of [2,5-dimethylfuran]-protected maleimides into polyamides such as peptides, peptide nucleic acids and peptoids were prepared, as well as the corresponding oligomers. Suitable maleimide deprotection conditions were established in each case. The stability of the adducts generated by Michael-type maleimide-thiol reaction and Diels-Alder cycloaddition to maleimide deprotection conditions was exploited to prepare a variety of conjugates from peptide and PNA scaffolds incorporating one free and one protected maleimide. The target molecules were synthesized by using two subsequent maleimide-involving click reactions separated by a maleimide deprotection step. Carrying out maleimide deprotection and conjugation simultaneously gave better results than performing the two reactions subsequently.

show abstract

Efficient method for the preparation of peptoids [oligo(N-substituted glycines)] by submonomer solid-phase synthesis

Cited by 1,190 publications

References 0 publications

Assembly and molecular order of two-dimensional peptoid nanosheets through the oil–water interface

Assembly and molecular order of two-dimensional peptoid nanosheets through the oil–water interface

Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides

Protected Maleimide Building Blocks for the Decoration of Peptides, Peptoids, and Peptide Nucleic Acids

Contact Info

Product

Resources

About