Self-assembly and hydrogelation of a potential bioactive peptide derived from quinoa proteins.

In this work the identification of peptides derived from quinoa proteins which could potentially self-assemble, and form hydrogels was carried out with TANGO, a statistical mechanical based algorithm that predicts β-aggregate propensity of peptides. Peptides with the highest aggregate propensity were subjected to gelling screening experiments from which the most promising bioactive peptide with sequence KIVLDSDDPLFGGF was selected. The self-assembling and hydrogelation properties of the C-terminal amidated peptide (KIVLDSDDPLFGGF-NH) were studied.

Recent developments in the cleavage, functionalization, and conjugation of proteins and peptides at tyrosine residues.

Peptide and protein selective modification at tyrosine residues has become an exploding field of research as tyrosine constitutes a robust alternative to lysine and cysteine-targeted traditional peptide/protein modification protocols. This review offers a comprehensive summary of the latest advances in tyrosine-selective cleavage, functionalization, and conjugation of peptides and proteins from the past three years. This updated overview complements the extensive body of work on site-selective modification of peptides and proteins, which holds significant relevance across various disciplines, including chemical, biological, medical, and material sciences.

Fabrication, characterization, and potential applications of re-assembled casein micelles.

Re-assembled casein micelles (CMs), were formulated in the 1970s as a model system to understand native casein micelles (CMs) in milk. These early works allowed an understanding of the critical factors involved in the formation of CMs, such as minerals (citrate, phosphate, and calcium), casein type (α-, β-, and κ-casein) and the extent of their phosphorylation. CMs were also used to understand the effect of treatments such as ethanol, high hydrostatic pressure and heating on the stability and integrity of the micelles.

A novel tyrosine hyperoxidation enables selective peptide cleavage.

A novel tyrosine hyperoxidation enabling selective peptide cleavage is reported. The scission of the N-terminal amide bond of tyrosine was achieved with Dess-Martin periodinane under mild conditions, generating a C-terminal peptide fragment bearing the unprecedented hyperoxidized tyrosine motif, 4,5,6,7-tetraoxo-1-indole-2-carboxamide, along with an intact N-terminal peptide fragment. This reaction proceeds with high site-selectivity for tyrosine and exhibits broad substrate scope for various peptides, including those containing post-translational modifications.

Synthesis and characterization of mono -lipidated peptide hydrogels: a platform for the preparation of reactive oxygen species responsive materials.

In this work we report the synthesis of mono lipidated peptides containing a 3-mercaptopropionate linker in the N-terminus by means of a photoinitiated thiol-ene reaction (S-lipidation). We evaluate the self-assembling and hydrogelation properties of a library of mono S-lipidated peptides containing lipid chains of various lengths and demonstrate that hydrogelation was driven by a balance between the lipid chain's hydrophobicity and the peptide's facial hydrophobicity. We further postulate that a simple calculation using estimated values of log D could be used as a predictor of hydrogelation when designing similar systems.

Nanoribbon self-assembly and hydrogel formation from an NOctanoyl octapeptide derived from the antiparallel β-Interface of a protein homotetramer.

The effect of installing different lipid chains (C, C, C, and C) on the N-terminus of an octapeptide derived from the antiparallel β-interface of the diaminopimelate decarboxylase protein homotetramer has been investigated. Notably, the C peptide conjugate assembled into wide twisted nanoribbons and formed hydrogels, which to the best of our knowledge constitutes the first example of a peptide containing an eight carbon alkyl chain that demonstrates these properties, a space typically occupied by peptide amphiphiles with long lipid chains. Furthermore, this self-assembling lipopeptide exhibited pH and temperature stability with shear thinning properties suitable for biomedical applications.

Directed self-assembly of peptide-diketopyrrolopyrrole conjugates - a platform for bio-organic thin film preparation.

Increased water solubility and long-range intermolecular ordering have been introduced into the fluorescent organic molecule thiophene-diketopyrrolopyrrole (TDPP) via its conjugation to the octapeptide HEFISTAH, which is derived from the protein-protein β-interface of the homo-tetramer protein diaminopimelate decarboxylase. The octapeptide, and its TDPP mono- and cross-linked conjugates were synthesised using 9-fluorenylmethoxycarbonyl (Fmoc) based solid-phase peptide synthesis (SPPS). Unlike the unmodified peptide, the resulting mono-linked and cross-linked peptides showed a fibrous morphology and formed hydrogels at 4 wt% in water at neutral pH, but failed to assemble at pH 2 and pH 9.

Design, characterization and evaluation of β-hairpin peptide hydrogels as a support for osteoblast cell growth and bovine lactoferrin delivery.

The use of peptide hydrogels is of growing interest in bone regeneration. Self-assembling peptides form hydrogels and can be used as injectable drug delivery matrices. Injected into the defect site, they can gel , and release factors that aid bone growth.

Structure-Activity Relationships of Wollamide Cyclic Hexapeptides with Activity against Drug-Resistant and Intracellular .

Wollamides are cyclic hexapeptides, recently isolated from an Australian soil isolate, that exhibit promising antimycobacterial activity against Bacille Calmette Guérin without displaying cytotoxicity against a panel of mammalian cells. Here, we report the synthesis and antimycobacterial activity of 36 new synthetic wollamides, collated with all known synthetic and natural wollamides, to reveal structure characteristics responsible for growth-inhibitory activity against (H37Rv, H37Ra, CDC1551, HN878, and HN353). The most potent antimycobacterial wollamides were those where residue VI d-Orn (wollamide B) was replaced by d-Arg (wollamide B1) or d-Lys (wollamide B2), with all activity being lost when residue VI was replaced by Gly, l-Arg, or l-Lys (wollamide B3).

Supramolecular Threading of Peptide Hydrogel Fibrils.

There is an increasing demand for biocompatible materials in biomedical applications. Herein, we report a modified α-helical decapeptide segment from the cardiac troponin C, which self-assembles into fibers with a secondary β-sheet structure. These fibers cross-link via a novel supramolecular threading mechanism which results in an atypical stiff hydrogel (' ≈ 13 kPa).

Total synthesis of the proposed structure of talarolide A.

The proposed structure of talarolide A, a cycloheptapeptide featuring a hydroxamate moiety within the peptide backbone, was successfully synthesized. An initial attempt to synthesize a linear peptide precursor containing a C-terminal N-benzyloxy glycine residue was problematic due to an unreported on-resin reduction of N-benzyloxy glycine to glycine. After repositioning the peptide cyclization point, a new linear peptide sequence was successfully prepared using Fmoc-solid-phase peptide synthesis.

Chemical Synthesis of Bioactive Naturally Derived Cyclic Peptides Containing Ene-Like Rigidifying Motifs.

The development of synthetic methods to prepare conformationally constrained peptides and peptide-polyketide hybrids remain an important chemical challenge. It is known that structural rigidity correlates with the specificity, bioactivity, and stability of these peptide systems, thus rigid systems are particularly attractive leads for development of potent biopharmaceuticals. Herein we provide an overview of recent developments in the syntheses of naturally derived constrained peptides and peptide-polyketide hybrids, with a particular emphasis on those systems containing an ene-like bond.

Understanding the metal mediated assembly and hydrogel formation of a β-hairpin peptide.

We report the design and characterization of a peptide that assembles as β-hairpins and forms hydrogels under physiological conditions. These hydrogels formed both in the absence and presence of several metal ions and displayed characteristic sheer-thinning properties. In particular, in the presence of Zn, we observed a novel hydrogel that proceeded via an intermolecular metal-coordination mechanism - intermolecular assembly that was previously reported instead to promote amyloid type aggregates.

Multifunctional thermoresponsive designer peptide hydrogels.

Unlabelled: We report the synthesis and characterization of multifunctional peptides comprised of a hydrogel forming β-sheet peptide segment and a matrix metalloproteinase 2 substrate containing a propargylglycinyl linker that is further derivatized with an RGD peptide sequence via "click" chemistry. In contrast to currently known systems, these multifunctional peptides formed gels that are stiffer than those formed by their respective precursors. All the peptides showed reversible thermoresponsive properties, which render them as suitable lead systems for a variety of possible biomedical applications.

Zinc-sensitive MRI contrast agent detects differential release of Zn(II) ions from the healthy vs. malignant mouse prostate.

Many secretory tissues release Zn(II) ions along with other molecules in response to external stimuli. Here we demonstrate that secretion of Zn(II) ions from normal, healthy prostate tissue is stimulated by glucose in fasted mice and that release of Zn(II) can be monitored by MRI. An ∼50% increase in water proton signal enhancement is observed in T1-weighted images of the healthy mouse prostate after infusion of a Gd-based Zn(II) sensor and an i.

Synthesis of Natural Cyclopentapeptides Isolated from Dianthus chinensis.

The first syntheses of the naturally occurring cyclic peptides dianthin I (1), pseudostellarin A (2), and heterophyllin J (3) are described. The linear protected peptide precursors were prepared efficiently via Fmoc-solid-phase synthesis and subsequently cyclized in solution under dilute conditions. The structures of the synthetic cyclopentapeptides were confirmed by NMR spectroscopy and mass spectrometry and were in agreement with the literature data reported for the natural products.

Structure-mechanical property correlations of hydrogel forming β-sheet peptides.

Peptide based hydrogels have received much attention due to their potential biomedical applications. The majority of the gel forming peptides present a β-sheet motif that is composed of alternating hydrophobic/hydrophilic amino acids. Furthermore, structural characterization of the assembly of these β-sheet peptides has been refined recently.

Design, synthesis, and characterization of new cyclic d,l-α-alternate amino acid peptides by capillary electrophoresis coupled to electrospray ionization mass spectrometry.

The self-assembly of peptide nanotubes (PNTs) depends on the structure and chemistry of cyclic peptide (CP) monomers, having an impact on their properties, making the choice of their monomers and their characterization a great challenge. We synthesized for the first time a new set of eight original CP sequences of 8, 10, and 12 d,l-α-alternate amino acids with a controlled internal diameter from 7 to 13 Å. They present various properties (e.

A peptide hydrogel derived from a fragment of human cardiac troponin C.

The human cardiac troponin C peptide fragment H-V(9)EQLTEEQKNEFKAAFDIFVLGA(31)-OH, which covers helix-A in the native protein, self-assembles into β-sheet fibrils in solution. These fibrils further entangle to give a hydrogel. This peptide may therefore serve as a template for development of novel biomaterials.

Synthesis and bioactivity of antitubercular peptides and peptidomimetics: an update.

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), an infection that has been declared a global public health emergency by the World Health Organization. Current anti-TB therapies are limited in their efficacy and have failed to prevent the spread of TB, due to the long term drug compliance required and the genesis of multidrug-resistant strains (MDR). The number of chemotherapeutic agents currently available to treat MDR is limited, therefore there is a great need for new anti-TB drugs.

An update on new methods to synthesize cyclotetrapeptides.

Cyclotetrapeptides are important bioactive lead drug molecules that display a wide spectrum of pharmacological activities. However, the synthesis of cyclotetrapeptides from their linear precursors is challenging due to the highly constrained conformation required for cyclisation, thus hampering their progress to a clinical setting. This review provides an account of the reported methods used for the synthesis of cyclotetrapeptides.

Basic MR relaxation mechanisms and contrast agent design.

The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists, largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities.

Design and biological evaluation of ⁹⁹mTc-N₂S₂-Tat(49-57)-c(RGDyK): a hybrid radiopharmaceutical for tumors expressing α(v)β(3) integrins.

Unlabelled: The α(ν)β(3) integrin is over-expressed in the tumor neovasculature and the tumor cells of glioblastomas. The HIV Tat-derived peptide has been used to deliver various cargos into cells. The aim of this research was to synthesize and assess the in vitro and in vivo uptake of (99m)Tc-N₂S₂-Tat(49-57)-c(RGDyK) ((99m)Tc-Tat-RGD) in α(ν)β(3) integrin positive cancer cells and compare it to that of a conventional (99m)Tc-RGD peptide ((99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2).

Effect of antimicrobial peptides derived from human cathelicidin LL-37 on Entamoeba histolytica trophozoites.

The human cathelicidin hCAP18/LL-37 is an antimicrobial protein consisting of a conserved N-terminal prosequence called the cathelin-like domain and a C-terminal peptide called LL-37. This peptide contains 37 amino acid residues, and several truncated variants obtained from natural sources or by chemical synthesis differ in their capability to damage Gram positive and Gram negative bacteria as well as Candida albicans. KR-12 is the shortest peptide (12 amino acids) of LL-37 that has conserved antibacterial activity.