Peptides are increasingly emerging as a drug class for a wide range of human diseases due to their intrinsic properties, such as excellent recognition abilities and biocompatibility ....
The widespread ability of proteins and peptides to self‐assemble by forming cross‐β structure is one of the most significant discoveries in structural biology. Intriguingly, the cross‐β association ...of proteins/peptides may generate intricate supramolecular architectures with uncommon spectroscopic properties. We have recently characterized self‐assembled peptides extracted from the PREP1 protein that are endowed with interesting structural/spectroscopic properties. We here demonstrate that the green fluorescence emission of the peptide PREP1117‐132 (λem ~520 nm), can be induced by excitation with UV radiation. The associated unusually large Stokes shift (Δλ ~150 nm) represents, to the best of our knowledge, the first evidence of an internal resonance energy transfer in amyloid‐like structures, where the blue emission of some assemblies becomes the excitation radiation for others. Moreover, the characterization of PREP1117‐132 variants provides insights into the sequence/structure and structure/spectroscopic properties relationships. Our data suggests that the green fluorescence is plausibly associated with antiparallel β‐sheet states of the peptide whereas parallel β‐sheet assemblies are only endowed with blue fluorescence. Notably, the different PREP1117‐132 variants also form assemblies characterized by distinct morphologies. Indeed, the parent peptide and single mutants form compact but structured aggregates whereas most of the double mutants exhibit elongated and highly extended fibers.
The characterization of an amyloid‐like cross‐β peptide demonstrates that it can emit visible fluorescence with unusual redshifts via a Foster resonance electron transfer (FRET) phenomenon and highlights interesting correlations between structural and spectroscopic properties.
Antibodies and antibody-derived molecules are continuously developed as both therapeutic agents and key reagents for advanced diagnostic investigations. Their application in these fields has indeed ...greatly expanded the demand of these molecules and the need for their production in high yield and purity. While full-length antibodies require mammalian expression systems due to the occurrence of functionally and structurally important glycosylations, most antibody fragments and antibody-like molecules are non-glycosylated and can be more conveniently prepared in
-based expression platforms. We propose here an updated survey of the most effective and appropriate methods of preparation of antibody fragments that exploit
as an expression background and review the pros and cons of the different platforms available today. Around 250 references accompany and complete the review together with some lists of the most important new antibody-like molecules that are on the market or are being developed as new biotherapeutics or diagnostic agents.
PREP1-based peptides form amyloid-like aggregates endowed with an intrinsic blue-green-red fluorescence with an unusual sharp maximum at 520 nm upon excitation with visible light under physiological ...conditions. The peptide PREP1117-132, whose sequence does not contain aromatic residues, presents a pH-dependent and reversible fluorescence, in line with its structural transition from β-sheet rich aggregates to α-helix structures. These findings further demonstrate that the non-canonical fluorescence exhibited by amyloids is an articulated phenomenon.
Recent Applications of Retro-Inverso Peptides Doti, Nunzianna; Mardirossian, Mario; Sandomenico, Annamaria ...
International journal of molecular sciences,
08/2021, Letnik:
22, Številka:
16
Journal Article
Recenzirano
Odprti dostop
Natural and de novo designed peptides are gaining an ever-growing interest as drugs against several diseases. Their use is however limited by the intrinsic low bioavailability and poor stability. To ...overcome these issues retro-inverso analogues have been investigated for decades as more stable surrogates of peptides composed of natural amino acids. Retro-inverso peptides possess reversed sequences and chirality compared to the parent molecules maintaining at the same time an identical array of side chains and in some cases similar structure. The inverted chirality renders them less prone to degradation by endogenous proteases conferring enhanced half-lives and an increased potential as new drugs. However, given their general incapability to adopt the 3D structure of the parent peptides their application should be careful evaluated and investigated case by case. Here, we review the application of retro-inverso peptides in anticancer therapies, in immunology, in neurodegenerative diseases, and as antimicrobials, analyzing pros and cons of this interesting subclass of molecules.
Integrating multi-responsive polymers such as microgels onto optical fiber tips, in a controlled fashion, enables unprecedented functionalities to Lab-on-fiber optrodes. The creation of a uniform ...microgel monolayer with a specific coverage factor is crucial for enhancing the probes responsivity to a pre-defined target parameter. Here we report a reliable fabrication strategy, based on the dip coating technique, for the controlled realization of microgel monolayer onto unconventional substrates, such as the optical fiber tip. The latter was previously covered by a plasmonic nanostructure to make it sensitive to superficial environment changes. Microgels have been prepared using specific Poly(
-isopropylacrylamide)-based monomers that enable bulky size changes in response to both temperature and pH variations. The formation of the microgel monolayer is efficiently controlled through the selection of suitable operating pH, temperature and concentration of particle dispersions used during the dipping procedure. The effect of each parameter has been evaluated, and the validity of our procedure is confirmed by means of both morphological and optical characterizations. We demonstrate that when the coverage factor exceeds 90%, the probe responsivity to microgels swelling/collapsing is significantly improved. Our study opens new paradigms for the development of engineered microgels assisted Lab-on-Fiber probes for biochemical applications.
Monoclonal Antibodies (mAbs) represent one of the most important classes of biotherapeutic agents. They are used to cure many diseases, including cancer, autoimmune diseases, cardiovascular diseases, ...angiogenesis-related diseases and, more recently also haemophilia. They can be highly varied in terms of format, source, and specificity to improve efficacy and to obtain more targeted applications. This can be achieved by leaving substantially unchanged the basic structural components for paratope clustering.
The objective was to trace the most relevant findings that have deserved prestigious awards over the years, to report the most important clinical applications and to emphasize their latest emerging therapeutic trends.
We report the most relevant milestones and new technologies adopted for antibody development. Recent efforts in generating new engineered antibody-based formats are briefly reviewed. The most important antibody-based molecules that are (or are going to be) used for pharmacological practice have been collected in useful tables.
The topics here discussed prove the undisputed role of mAbs as innovative biopharmaceuticals molecules and as vital components of targeted pharmacological therapies.
IL-36 cytokines, a subgroup of IL-1 family, comprise IL-36α, IL-36β, and IL-36γ agonists, abundantly expressed in psoriatic skin, and IL-36RA and IL-38 antagonists. In psoriatic skin, IL-36 cytokines ...interfere with keratinocyte cornification programs and induce the release of antimicrobial peptides and chemokines active on neutrophils and Th17 lymphocytes. To date, the role of IL-38 antagonist in psoriasis remains to be defined. Here, we demonstrate that skin and circulating IL-38 levels are reduced in psoriatic patients and in other skin diseases characterized by neutrophilic infiltrate. In psoriasis, the balance of IL-36γ agonist/IL-38 antagonist serum levels is in favor of agonists and is closely associated with disease severity. Interestingly, IL-38 is upregulated by anti-IL-17A biological treatment and positively correlates with the therapeutic efficacy of secukinumab in psoriatic patients. The downregulation of IL-38 expression is strictly related to keratinocyte de-differentiation triggered by the inflammatory cytokines IL-36γ, IL-17, and IL-22. Finally, we demonstrate that administration of recombinant full-length IL-38 counteracts in vitro the biological processes induced by IL-36γ in human keratinocytes and endothelial cells and attenuates in vivo the severity of the psoriasiform phenotype induced by IMQ in mice. Such effects are achieved by restoring the physiological programs of keratinocyte proliferation and differentiation, and reducing the immune cell infiltrates.
Microgels (MGs) are synthetic colloidal hydrogel particles made of three dimensional polymer networks. Their chemical composition is crucial for their use as intelligent drug release systems operated ...by temperature control. Herein, several MGs using N‐isopropylacrylamide (Nipam)/N‐isopropylmethacrylamide (Nipmam), chitosan and acrylic/methacrylic acid have been synthesized by free radical polymerization reactions (NC MGs) and the effects of surfactants and different reaction times on size and swelling properties have been investigated. MGs have been identified and characterized by dynamic light scattering and atomic force microscopy, and finally used to optimize the encapsulation protocol of the hydrophobic drug sorafenib. The drug delivery system here described has encapsulation efficiency of 40% and releases 10% of the entrapped drug over about 16 h after the temperature is raised above the volume phase transition temperature. Data suggest that MGs with optimized composition may act as properly instructed entities able to trap and release biomolecules following external stimuli.
Amyloid aggregation is a widespread process that involves proteins and peptides with different molecular complexity and amino acid composition. The structural motif (cross-β) underlying this ...supramolecular organization generates aggregates endowed with special mechanical and spectroscopic properties with huge implications in biomedical and technological fields, including emerging precision medicine. The puzzling ability of these assemblies to emit intrinsic and label-free fluorescence in regions of the electromagnetic spectrum, such as visible and even infrared, usually considered to be forbidden in the polypeptide chain, has attracted interest for its many implications in both basic and applied science. Despite the interest in this phenomenon, the physical basis of its origin is still poorly understood. To gain a global view of the available information on this phenomenon, we here provide an exhaustive survey of the current literature in which original data on this fluorescence have been reported. The emitting systems have been classified in terms of their molecular complexity, amino acid composition, and physical state. Information about the wavelength of the radiation used for the excitation as well as the emission range/peak has also been retrieved. The data collected here provide a picture of the complexity of this multifaceted phenomenon that could be helpful for future studies aimed at defining its structural and electronic basis and/or stimulating new applications.
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