Boosting stability: a hierarchical approach for self-assembling peptide structures.

The primary objective of this study was to implement a hierarchical approach to enhance the conformational stability of a selected group of peptides by incorporating -(1,2)-2-aminocyclopentanecarboxylic acid (-ACPC). The influence of residue mutation on the peptide structures was investigated using circular dichroism, analytical ultracentrifugation, and vibrational spectroscopy. The resulting nanostructures were examined transmission electron microscopy.

Challenges in Peptide Solubilization - Amyloids Case Study.

Peptide science has been a rapidly growing research field because of the enormous potential application of these biocompatible and bioactive molecules. However, many factors limit the widespread use of peptides in medicine, and low solubility is among the most common problems that hamper drug development in the early stages of research. Solubility is a crucial, albeit poorly understood, feature that determines peptide behavior.

Cytotoxic PSMα3 inhibits the aggregation of human insulin .

Phenol-soluble modulins (PSMs) are extracellular short amphipathic peptides secreted by the bacteria (). They play an essential role in the bacterial lifecycle, biofilm formation, and stabilisation. From the PSM family, PSMα3 has been of special interest recently due to its cytotoxicity and highly stable α-helical conformation, which also remains in its amyloid fibrils.

Structural effects of charge destabilization and amino acid substitutions in amyloid fragments of CsgA.

The most studied functional amyloid is the CsgA, major curli subunit protein, which is produced by numerous strains of Enterobacteriaceae. Although CsgA sequences are highly conserved, they exhibit species diversity, which reflects the specific evolutionary and functional adaptability of the major curli subunit. Herein, we performed bioinformatics analyses to uncover the differences in the amyloidogenic properties of the R4 fragments in Escherichia coli and Salmonella enterica and proposed four mutants for more detailed studies: M1, M2, M3, and M4.

PACT - Prediction of amyloid cross-interaction by threading.

Amyloid proteins are often associated with the onset of diseases, including Alzheimer's, Parkinson's and many others. However, there is a wide class of functional amyloids that are involved in physiological functions, e.g.

Hybrid Zn-β-Aminoporphyrin-Carbon Nanotubes: Pyrrolidine and Direct Covalent Linkage Recognition, and Multiple-Photo Response.

To unveil and shape the molecular connectivity in (metallo)porphyrin-carbon nanotube hybrids are of main relevance for the multiple medicinal, photoelectronic, catalytic, and photocatalytic applications of these materials. Multi-walled carbon nanotubes (MWCNTs) were modified through 1,3-dipolar cycloaddition reactions with azomethine ylides generated in situ and carrying pentafluorophenyl groups, followed by immobilization of the β-amino-tetraphenylporphyrinate Zn(II). The functionalities were confirmed via XPS and FTIR, whereas Raman spectroscopy showed disruptions on the graphitic carbon nanotube surface upon both steps.

The application of the hierarchical approach for the construction of foldameric peptide self-assembled nanostructures.

In this paper, we show that a hierarchical approach for the construction of nanofibrils based on α,β-peptide foldamers is a rational method for the design of novel self-assembled nanomaterials based on peptides. Incorporation of a -(1,2)-2-aminocyclopentanecarboxylic acid residue into the outer positions of the model coiled-coil peptide led to the formation of helical foldamers, which was determined by circular dichroism (CD) and vibrational spectroscopy. The oligomerization state of the obtained peptides in water was established by analytical ultracentrifugation (AUC).

Exploring a diverse world of effector domains and amyloid signaling motifs in fungal NLR proteins.

NLR proteins are intracellular receptors constituting a conserved component of the innate immune system of cellular organisms. In fungi, NLRs are characterized by high diversity of architectures and presence of amyloid signaling. Here, we explore the diverse world of effector and signaling domains of fungal NLRs using state-of-the-art bioinformatic methods including MMseqs2 for fast clustering, probabilistic context-free grammars for sequence analysis, and AlphaFold2 deep neural networks for structure prediction.

Controlling the conformational stability of coiled-coil peptides with a single stereogenic center of a peripheral β-amino acid residue.

The key issue in the research on foldamers remains the understanding of the relationship between the monomers structure and conformational properties at the oligomer level. In peptidomimetic foldamers, the main goal of which is to mimic the structure of proteins, a main challenge is still better understanding of the folding of peptides and the factors that influence their conformational stability. We probed the impact of the modification of the peptide periphery with - and -2-aminocyclopentanecarboxylic acid (ACPC) on the structure and stability of the model coiled-coil using circular dichroism (CD), analytical ultracentrifugation (AUC) and two-dimensional nuclear magnetic resonance spectroscopy (2D NMR).

Challenges in Experimental Methods.

Experimental studies of amyloids encounter many challenges. There are many methods available for studying proteins, which can be applied to amyloids: from basic staining techniques, allowing visualization of fibers, to complex methods, e.g.

Peptide foldamer-based self-assembled nanostructures containing cyclic beta-amino acids.

Peptide soft materials belong to an emerging branch of materials sciences due to their growing importance as responsive materials in diagnostics, therapeutics, and biomedical applications. The diversity provided by easily modifiable peptide sequences can be further increased by introducing nonnatural amino acids such as cyclic β-amino acids, leading to the formation of foldamers. Moreover, it is possible to combine peptide chains with other polymers, aromatic compounds, etc.

Variability of Amyloid Propensity in Imperfect Repeats of CsgA Protein of and .

CsgA is an aggregating protein from bacterial biofilms, representing a class of functional amyloids. Its amyloid propensity is defined by five fragments (R1-R5) of the sequence, representing non-perfect repeats. Gate-keeper amino acid residues, specific to each fragment, define the fragment's propensity for self-aggregation and aggregating characteristics of the whole protein.

Searching for universal model of amyloid signaling motifs using probabilistic context-free grammars.

Background: Amyloid signaling motifs are a class of protein motifs which share basic structural and functional features despite the lack of clear sequence homology. They are hard to detect in large sequence databases either with the alignment-based profile methods (due to short length and diversity) or with generic amyloid- and prion-finding tools (due to insufficient discriminative power). We propose to address the challenge with a machine learning grammatical model capable of generalizing over diverse collections of unaligned yet related motifs.

Hierarchical approach for the rational construction of helix-containing nanofibrils using α,β-peptides.

The rational design of novel self-assembled nanomaterials based on peptides remains a great challenge in modern chemistry. A hierarchical approach for the construction of nanofibrils based on α,β-peptide foldamers is proposed. The incorporation of a helix-promoting trans-(1S,2S)-2-aminocyclopentanecarboxylic acid residue in the outer positions of the model coiled-coil peptide led to its increased conformational stability, which was established consistently by the results of CD, NMR and FT-IR spectroscopy.

Controlling the Helix Handedness of ααβ-Peptide Foldamers through Sequence Shifting.

Peptide foldamers containing both cis-β-aminocyclopentanecarboxylic acid and α-amino acid residues combined in various sequence patterns (ααβ, αααβ, αβααβ, and ααβαααβ) were screened using CD and NMR spectroscopy for the tendency to form helices. ααβ-Peptides were found to fold into an unprecedented and well-defined 16/17/15/18/14/17-helix. By extending the length of the sequence or shifting a fragment of the sequence from one terminus to another in ααβ-peptides, the balance between left-handed and right-handed helix populations present in the solution can be controlled.

Progress in the Raman spectra analysis of covalently functionalized multiwalled carbon nanotubes: unraveling disorder in graphitic materials.

Raman spectroscopy is highly sensitive to the morphology and electronic structures of graphitic materials, but a convenient interpretation model has been lacking for multiwalled carbon nanotubes (MWCNTs), in particular for the discrimination of spectral changes induced by covalent functionalization. The present work describes a systematic investigation of the Raman analysis of covalently functionalized MWCNTs by diazonium chemistry and oxidation methodologies, with typically different mechanisms and reaction sites. A multi-peak deconvolution system and spectral band assignment were proposed based on the chemical and structural modifications identified by X-ray photoelectron spectroscopy, thermogravimetry, X-ray diffraction, specific surface areas and the comparative analysis of the first and second order regions of the Raman spectra.