Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structural Diversity of Peptoids: Tube-Like Structures of Macrocycles.

ABSTRACT: Peptoids, or poly-N-substituted glycines, are characterised by broad structural diversity. Compared to peptides, they are less restricted in rotation and lack backbone-derived H bonding. Nevertheless, certain side chains force the peptoid backbone into distinct conformations. Designable secondary structures like helices or nanosheets arise from this knowledge. Herein, we report the copper-catalysed alkyne-azide cycloaddition (CuAAC) of macrocycles to form innovative tube-like tricyclic peptoids, giving access to host-guest chemistry or storage applications. Different linker systems make the single tubes tuneable in size and enable modifications within the gap. An azobenzene linker, which is reversibly switchable in conformation, was successfully incorporated and allowed for light-triggered changes of the entire tricyclic structure.

SUBMITTER: Herlan CN

PROVIDER: S-EPMC7795174 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Structural Diversity of Peptoids: Tube-Like Structures of Macrocycles.

Herlan Claudine Nicole CN Sommer Katharina K Weis Patrick P Nieger Martin M Bräse Stefan S

Molecules (Basel, Switzerland) 20201231 1

Peptoids, or poly-<i>N</i>-substituted glycines, are characterised by broad structural diversity. Compared to peptides, they are less restricted in rotation and lack backbone-derived H bonding. Nevertheless, certain side chains force the peptoid backbone into distinct conformations. Designable secondary structures like helices or nanosheets arise from this knowledge. Herein, we report the copper-catalysed alkyne-azide cycloaddition (CuAAC) of macrocycles to form innovative tube-like tricyclic pe ...[more]

PMID: 33396246

Similar Datasets

Expanding structural diversity in a library of disulfide macrocycles through in-situ imide hydrolysis.

Project description:We describe here an unorthodox approach to dynamic covalent chemistry in which the initially-unexpected in-situ hydrolysis of a bis-imide is employed to control the composition of a library of structurally diverse macrocycles. A single building block is used to generate a library of numerous disulfide-based architectures in a one-pot single-step process. The dual-stimuli method is based on simultaneous changes in pH and DMSO concentration to expand the structural diversity of the macrocyclic products. Mechanistic details of this complex process are investigated by the kinetics analysis. We delivered a facile strategy for the synthesis of water-soluble, multicomponent and dynamic macrocycles equipped with number of different functional groups, thus giving a prospect of their application in guest-driven phase transfer.

| S-EPMC8742088 | biostudies-literature

Crystal structures of two cross-bridged chromium(III) tetra-aza-macrocycles.

Project description:The crystal structure of di-chlorido-(4,10-dimethyl-1,4,7,10-tetra-aza-bicyclo-[5.5.2]tetra-deca-ne)chromium(III) hexa-fluorido-phosphate, [CrCl2(C12H26N4)]PF6, (I), has monoclinic symmetry (space group P21/n) at 150 K. The structure of the related di-chlorido-(4,11-dimethyl-1,4,8,11-tetra-aza-bicyclo-[6.6.2]hexa-deca-ne)chromium(III) hexa-fluorido-phosphate, [CrCl2(C14H30N4)]PF6, (II), also displays monoclinic symmetry (space group P21/c) at 150 K. In each case, the Cr(III) ion is hexa-coordinate with two cis chloride ions and two non-adjacent N atoms bound cis equatorially and the other two non-adjacent N atoms bound trans axially in a cis-V conformation of the macrocycle. The extent of the distortion from the preferred octa-hedral coordination geometry of the Cr(III) ion is determined by the parent macrocycle ring size, with the larger cross-bridged cyclam ring in (II) better able to accommodate this preference and the smaller cross-bridged cyclen ring in (I) requiring more distortion away from octa-hedral geometry.

| S-EPMC4186087 | biostudies-literature

Structural diversity and phylogenetic distribution of valyl tRNA-like structures in viruses.

Project description:Viruses commonly use specifically folded RNA elements that interact with both host and viral proteins to perform functions important for diverse viral processes. Examples are found at the 3' termini of certain positive-sense ssRNA virus genomes where they partially mimic tRNAs, including being aminoacylated by host cell enzymes. Valine-accepting tRNA-like structures (TLSVal) are an example that share some clear homology with canonical tRNAs but have several important structural differences. Although many examples of TLSVal have been identified, we lacked a full understanding of their structural diversity and phylogenetic distribution. To address this, we undertook an in-depth bioinformatic and biochemical investigation of these RNAs, guided by recent high-resolution structures of a TLSVal We cataloged many new examples in plant-infecting viruses but also in unrelated insect-specific viruses. Using biochemical and structural approaches, we verified the secondary structure of representative TLSVal substrates and tested their ability to be valylated, confirming previous observations of structural heterogeneity within this class. In a few cases, large stem-loop structures are inserted within variable regions located in an area of the TLS distal to known host cell factor binding sites. In addition, we identified one virus whose TLS has switched its anticodon away from valine, causing a loss of valylation activity; the implications of this remain unclear. These results refine our understanding of the structural and functional mechanistic details of tRNA mimicry and how this may be used in viral infection.

| S-EPMC7749636 | biostudies-literature

Mechanism and structural diversity of exoribonuclease-resistant RNA structures in flaviviral RNAs.

Project description:Flaviviruses such as Yellow fever, Dengue, West Nile, and Zika generate disease-linked viral noncoding RNAs called subgenomic flavivirus RNAs. Subgenomic flavivirus RNAs result when the 5'-3' progression of cellular exoribonuclease Xrn1 is blocked by RNA elements called Xrn1-resistant RNAs located within the viral genome's 3'-untranslated region that operate without protein co-factors. Here, we show that Xrn1-resistant RNAs can halt diverse exoribonucleases, revealing a mechanism in which they act as general mechanical blocks that 'brace' against an enzyme's surface, presenting an unfolding problem that confounds further enzyme progression. Further, we directly demonstrate that Xrn1-resistant RNAs exist in a diverse set of flaviviruses, including some specific to insects or with no known arthropod vector. These Xrn1-resistant RNAs comprise two secondary structural classes that mirror previously reported phylogenic analysis. Our discoveries have implications for the evolution of exoribonuclease resistance, the use of Xrn1-resistant RNAs in synthetic biology, and the development of new therapies.

| S-EPMC5760640 | biostudies-literature

A diversity-oriented synthesis approach to macrocycles via oxidative ring expansion.

Project description:Macrocycles are key structural elements in numerous bioactive small molecules and are attractive targets in the diversity-oriented synthesis of natural product-based libraries. However, efficient and systematic access to diverse collections of macrocycles has proven difficult using classical macrocyclization reactions. To address this problem, we have developed a concise, modular approach to the diversity-oriented synthesis of macrolactones and macrolactams involving oxidative cleavage of a bridging double bond in polycyclic enol ethers and enamines. These substrates are assembled in only four or five synthetic steps and undergo ring expansion to afford highly functionalized macrocycles bearing handles for further diversification. In contrast to macrocyclization reactions of corresponding seco acids, the ring expansion reactions are efficient and insensitive to ring size and stereochemistry, overcoming key limitations of conventional approaches to systematic macrocycle synthesis. Cheminformatic analysis indicates that these macrocycles access regions of chemical space that overlap with natural products, distinct from currently targeted synthetic drugs.

| S-EPMC3359144 | biostudies-literature

Structural and Spectroscopic Properties of Assemblies of Self-Replicating Peptide Macrocycles.

Project description:Self-replication at the molecular level is often seen as essential to the early origins of life. Recently a mechanism of self-replication has been discovered in which replicator self-assembly drives the process. We have studied one of the examples of such self-assembling self-replicating molecules to a high level of structural detail using a combination of computational and spectroscopic techniques. Molecular Dynamics simulations of self-assembled stacks of peptide-derived replicators provide insights into the structural characteristics of the system and serve as the basis for semiempirical calculations of the UV-vis, circular dichroism (CD) and infrared (IR) absorption spectra that reflect the chiral organization and peptide secondary structure of the stacks. Two proposed structural models are tested by comparing calculated spectra to experimental data from electron microscopy, CD and IR spectroscopy, resulting in a better insight into the specific supramolecular interactions that lead to self-replication. Specifically, we find a cooperative self-assembly process in which ?-sheet formation leads to well-organized structures, while also the aromatic core of the macrocycles plays an important role in the stability of the resulting fibers.

| S-EPMC5616102 | biostudies-literature

Structural and non-structural genes contribute to the genetic diversity of RNA viruses

Project description:With the advent of advanced sequencing technology, studies of RNA viruses have shown that genetic diversity contribute to both attenuation and virulence. The differences in genetic diversity of wild-type Asibi virus and 17D-204 vaccine provides an unique opportunity to investigate RNA population theory in the context of a well described live attenuated vaccine. Utilizing infectious clone-derived viruses containing some of the amino acid substitutions that differentiate yellow fever wild-type Asibi strain from 17D vaccine and recovered in a controlled experiment, establishes that the genetic diversity differences that exist between wild-type Asibi and 17D-204 vaccine viruses are not influenced by either different passage history or source of samples, but rather resulted from the attenuation of wild-type Asibi virus to yield the 17D vaccine sub-strains.

2018-10-16 | E-MTAB-6614 | biostudies-arrayexpress

A Multidimensional Diversity-Oriented Synthesis Strategy for Structurally Diverse and Complex Macrocycles.

Project description:Synthetic macrocycles are an attractive area in drug discovery. However, their use has been hindered by a lack of versatile platforms for the generation of structurally (and thus shape) diverse macrocycle libraries. Herein, we describe a new concept in library synthesis, termed multidimensional diversity-oriented synthesis, and its application towards macrocycles. This enabled the step-efficient generation of a library of 45 novel, structurally diverse, and highly-functionalized macrocycles based around a broad range of scaffolds and incorporating a wide variety of biologically relevant structural motifs. The synthesis strategy exploited the diverse reactivity of aza-ylides and imines, and featured eight different macrocyclization methods, two of which were novel. Computational analyses reveal a broad coverage of molecular shape space by the library and provides insight into how the various diversity-generating steps of the synthesis strategy impact on molecular shape.

| S-EPMC5025730 | biostudies-literature

Structure-function relationships in peptoids: recent advances toward deciphering the structural requirements for biological function.

Project description:Oligomers of N-substituted glycine, or peptoids, are versatile tools to probe biological processes and hold promise as therapeutic agents. An underlying theme in the majority of recent peptoid research is the connection between peptoid function and peptoid structure. For certain applications, well-folded peptoids are essential for activity, while unstructured peptoids appear to suffice, or even are superior, for other applications. Currently, these structure-function connections are largely made after the design, synthesis, and characterization process. However, as guidelines for peptoid folding are elucidated and the known biological activities are expanded, we anticipate these connections will provide a pathway toward the de novo design of functional peptoids. In this perspective, we review several of the peptoid structure-function relationships that have been delineated over the past five years.

| S-EPMC5962266 | biostudies-literature

Antifouling glycocalyx-mimetic peptoids.

Project description:The glycocalyx of the cell is composed of highly hydrated saccharidic groups conjugated to protein and lipid cores. Although components of the glycocalyx are important in cell-cell interactions and other specific biological recognition events, a fundamental role of the glycocalyx is the inhibition of nonspecific interactions at the cell surface. Inspired by glycoproteins present in the glycocalyx, we describe a new class of synthetic antifouling polymer composed of saccharide containing N-substituted polypeptide (glycopeptoid). Grafting of glycopeptoids to a solid surface resulted in a biomimetic shielding layer that dramatically reduced nonspecific protein, fibroblast, and bacterial cell attachment. All-atom molecular dynamics simulation of grafted glycopeptoids revealed an aqueous interface enriched in highly hydrated saccharide residues. In comparison to saccharide-free peptoids, the interfacial saccharide residues of glycopeptoids formed a higher number of hydrogen bonds with water molecules. Moreover, these hydrogen bonds displayed a longer persistence time, which we believe contributed to fouling resistance by impeding interactions with biomolecules. Our findings suggest that the fouling resistance of glycopeptoids can be explained by the presence of both a 'water barrier' effect associated with the hydrated saccharide residues as well as steric hindrance from the polymer backbone.

| S-EPMC3807125 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data