A Systematic Review of Antiamyloidogenic and Metal-Chelating Peptoids: Two Structural Motifs for the Treatment of Alzheimer’s Disease

Young, Sherri C.

doi:10.3390/molecules23020296

Cited by 12 publications

(5 citation statements)

References 71 publications

(128 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One such approach takes advantage of peptoids that can serve as ligands for targeted metal coordination. [85][86][87][88][89] However, there are limited reports on metallopeptoids with atomically-defined structure in solution. The first examples of atomic structures of metallopeptoids were characterized in the solid-state using crystallography and not in solution.…”

Section: Engineering the Atomic Structure Of Peptoid Chain Conformationmentioning

confidence: 99%

Engineering the atomic structure of sequence-defined peptoid polymers and their assemblies

Xuan

Zuckermann

2020

Polymer

View full text Add to dashboard Cite

Peptoids are a family of sequence-defined, non-natural biomimetic polymers which show excellent properties including good chemical and enzymatic stability and high structural tunability. The solid-phase submonomer synthesis method allows precise control over the identity and sequence of chemically diverse side chains, enabling the atomic engineering of their chemical structures for a variety of applications. This unprecedented level of structural control enables access to atomically defined threedimensional chain conformations and assemblies, facilitating the design and optimization of a variety of nanoscale architectures that can function in biology and materials science. In order to approach the rational design of peptoid materials in a more predictive and precise manner, it is crucial to fully understand how chemical information, in the form of the monomer sequence, encodes their folding and assembly into structurally defined, functional 3D shapes. This perspective focuses on recent studies into the atomic engineering of peptoid nanostructures by examining the impact of sequence variations on their secondary and three-dimensional structures, as well as their functional properties.

show abstract

Section: Engineering the Atomic Structure Of Peptoid Chain Conformationmentioning

confidence: 99%

Engineering the atomic structure of sequence-defined peptoid polymers and their assemblies

Xuan

Zuckermann

2020

Polymer

View full text Add to dashboard Cite

show abstract

“…While these insights have led to development of individual drug‐design strategies, the interplay between these spaces remains largely unstudied. In addition to novel antimicrobial agents, peptoid membrane‐based mechanisms revealed by X‐ray scattering are applicable for treatment of cancer, and neurodegenerative diseases . We anticipate future optimizations into peptoids as therapeutics to be guided by more complex systems of membrane mimetics such as surface X‐ray scattering of supported lipid bilayers, mixtures of lipids, and inclusion of components from mammalian cytoskeleton and bacterial cell walls.…”

Section: Future Prospectsmentioning

confidence: 99%

Peptoid drug discovery and optimization via surface X‐ray scattering

2019

View full text Add to dashboard Cite

Synthetic polymers mimicking antimicrobial peptides have drawn considerable interest as potential therapeutics. N‐substituted glycines, or peptoids, are recognized by their in vivo stability and ease of synthesis. Peptoids are thought to act primarily on the negatively charged lipids that are abundant in bacterial cell membranes. A mechanistic understanding of lipid–peptoid interaction at the molecular level will provide insights for rational design and optimization of peptoids. Here, we highlight recent studies that utilize synchrotron liquid surface X‐ray scattering to characterize the underlying peptoid interactions with bacterial and eukaryotic membranes. Cellular membranes are highly complex, and difficult to characterize at the molecular level. Model systems including Langmuir monolayers, are used in these studies to reduce system complexity. The general workflow of these systems and the corresponding data analysis techniques are presented alongside recent findings. These studies investigate the role of peptoid physicochemical characteristics on membrane activity. Specifically, the roles of cationic charge, conformational constraint via macrocyclization, and hydrophobicity are shown to correlate their membrane interactions to biological activities in vitro. These structure–activity relationships have led to new insights into the mechanism of action by peptoid antimicrobials, and suggest optimization strategies for future therapeutics based on peptoids.

show abstract

“…Peptoid modifications are straightforward and have moderate clearance [41]. Therefore, we believe peptoids can serve as a drug-like, biologically amenable, and economical class of molecules [35,[42][43][44][45] that may be developed into effective therapeutics or formulations of nasal sprays or eye drops.…”

Section: Introductionmentioning

confidence: 99%

“Molecular Masks” for ACE2 to Effectively and Safely Block SARS-CoV-2 Virus Entry

Shukla

Rustagi

Gao

et al. 2021

IJMS

View full text Add to dashboard Cite

Coronavirus Disease 2019 (COVID-19) remains a global health crisis, despite the development and success of vaccines in certain countries. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, uses its spike protein to bind to the human cell surface receptor angiotensin-converting enzyme 2 (ACE2), which allows the virus to enter the human body. Using our unique cell screening technology, we identified two ACE2-binding peptoid compounds and developed dimeric derivatives (ACE2P1D1 and ACE2P2D1) that effectively blocked spike protein-ACE2 interaction, resulting in the inhibition of SARS-CoV-2 pseudovirus entry into human cells. ACE2P1D1 and ACE2P2D1 also blocked infection by a D614G mutant pseudovirus. More importantly, these compounds do not decrease ACE2 expression nor its enzyme activity (which is important in normal blood pressure regulation), suggesting safe applicability in humans

show abstract

A Systematic Review of Antiamyloidogenic and Metal-Chelating Peptoids: Two Structural Motifs for the Treatment of Alzheimer’s Disease

Cited by 12 publications

References 71 publications

Engineering the atomic structure of sequence-defined peptoid polymers and their assemblies

Engineering the atomic structure of sequence-defined peptoid polymers and their assemblies

Peptoid drug discovery and optimization via surface X‐ray scattering

“Molecular Masks” for ACE2 to Effectively and Safely Block SARS-CoV-2 Virus Entry

Contact Info

Product

Resources

About