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•Self-assembly of non-standard amino acids and peptide containing them.•Development of nanomaterials with a wide range of applications.•The digest provides an on overview based on ...amino acid modification.
The exploitation of peptides in the development of smart nanomaterials is gaining increasing attention in the last few years. Amino acids are indeed able to drive the self-assembly and the self-organization at the molecular level. By using non-standard amino acids, it is possible to expand the scope of the possible applications, ranging from biomaterials, biosensors to drug delivery systems. In this digest, the recent advances in this field are presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Despite the recent advances in lung cancer biology, molecular pathology, and treatment, this malignancy remains the leading cause of cancer-related death worldwide and non-small cell lung cancer ...(NSCLC) is the most common form found at diagnosis. Accurate staging of the disease is a fundamental prognostic factor that correctly predicts progression-free (PFS) and overall survival (OS) of NSCLC patients. However, outcome of patients within each TNM staging group can change widely highlighting the need to identify additional prognostic biomarkers to better stratify patients on the basis of risk. 18F-FDG PET/CT plays an essential role in staging, evaluation of treatment response, and tumoral target delineation in NSCLC patients. Moreover, a number of studies showed the prognostic role of imaging parameters derived from PET images, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG). These parameters represent three-dimensional PET-based measurements providing information on both tumor volume and metabolic activity and previous studies reported their ability to predict OS and PFS of NSCLC patients. This review will primarily focus on the studies that showed the prognostic and predictive role of MTV and TLG in NSCLC patients, addressing also their potential utility in the new era of immunotherapy of NSCLC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Alpha-synuclein (αSyn) is a highly expressed and conserved protein, typically found in the presynaptic terminals of neurons. The misfolding and aggregation of αSyn into amyloid fibrils is a ...pathogenic hallmark of several neurodegenerative diseases called synucleinopathies, such as Parkinson’s disease. Since αSyn is an Intrinsically Disordered Protein, the characterization of its structure remains very challenging. Moreover, the mechanisms by which the structural conversion of monomeric αSyn into oligomers and finally into fibrils takes place is still far to be completely understood. Over the years, various studies have provided insights into the possible pathways that αSyn could follow to misfold and acquire oligomeric and fibrillar forms. In addition, it has been observed that αSyn structure can be influenced by different parameters, such as mutations in its sequence, the biological environment (e.g., lipids, endogenous small molecules and proteins), the interaction with exogenous compounds (e.g., drugs, diet components, heavy metals). Herein, we review the structural features of αSyn (wild-type and disease-mutated) that have been elucidated up to present by both experimental and computational techniques in different environmental and biological conditions. We believe that this gathering of current knowledge will further facilitate studies on αSyn, helping the planning of future experiments on the interactions of this protein with targeting molecules especially taking into consideration the environmental conditions.
Lysozyme (E.C. 3.2.1.17), an about 14 kDa protein and pI 11, widely spread in nature, is present in humans mainly in milk, saliva, and intestinal mucus as a part of innate defense mechanisms. It is ...endowed with antimicrobial activity due to its action as an N-acetylmuramidase, cleaving the 1-4β glycosidic linkage in the peptidoglycan layer of Gram-positive bacteria. This antimicrobial activity is exerted only against a limited number of Gram-negative bacteria. Different action mechanisms are proposed to explain its activity against Gram-negative bacteria, viruses, and fungi. The antiviral activity prompted the study of a possible application of lysozyme in the treatment of SARS-CoV-2 infections. Among the different sources of lysozyme, the chicken egg albumen was chosen, being the richest source of this protein (c-type lysozyme, 129 amino acids). Interestingly, the activity of lysozyme hydrochloride against SARS-CoV-2 was related to the heating (to about 100 °C) of this molecule. A chemical-physical characterization was required to investigate the possible modifications of native lysozyme hydrochloride by heat treatment. The FTIR analysis of the two preparations of lysozyme hydrochloride showed appreciable differences in the secondary structure of the two protein chains. HPLC and NMR analyses, as well as the enzymatic activity determination, did not show significant modifications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective
Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are imaging parameters derived from 18F-FDG PET/CT that have been proposed for risk stratification of cancer patients. The aim ...of our study was to test whether these whole-body volumetric imaging parameters may predict outcome in patients with non-small cell lung cancer (NSCLC).
Methods
Sixty-five patients (45 men, 20 women; mean age ± SD, 65 ± 12 years), with histologically proven NSCLC who had undergone 18F-FDG PET/CT scan before any therapy, were included in the study. Imaging parameters including SUV
max
, SUV
mean
, total MTV (MTV
TOT
) and whole-body TLG (TLG
WB
) were determined. Univariate and multivariate analyses of clinical and imaging variables were performed using Cox proportional hazards regression. Survival analysis was performed using Kaplan–Meier method and log-rank tests.
Results
A total of 298 lesions were analyzed including 65 primary tumors, 114 metastatic lymph nodes and 119 distant metastases. MTV
TOT
and TLG
WB
could be determined in 276 lesions. Mean value of MTV
TOT
was 81.83 ml ± 14.63 ml (SE) whereas mean value of TLG
WB
was 459.88 g ± 77.02 g (SE). Univariate analysis showed that, among the variables tested, primary tumor diameter (
p
= 0.0470), MTV of primary tumor (
p
= 0.0299), stage (
p
< 0.0001), treatment (
p
< 0.0001), MTV
TOT
(
p
= 0.0003) and TLG
WB
(
p
= 0.0002) predicted progression-free survival in NSCLC patients, while age (
p
= 0.0550), MTV of primary tumor (
p
= 0.0375), stage (
p
< 0.0001), treatment (
p
< 0.0001), MTV
TOT
(
p
= 0.0001) and TLG
WB
(
p
= 0.0008) predicted overall survival. At multivariate analysis age, TLG
WB
and stage were retained in the model for prediction of progression-free survival (
p
< 0.0001), while age, MTV
TOT
and stage were retained in the model for prediction of overall survival (
p
< 0.0001). Survival analysis showed that patients with TLG
WB
≤ 54.7 g had a significantly prolonged progression-free survival as compared to patients with TLG
WB
> 54.7 g (
p
< 0.0001). Moreover, overall survival was significantly better in patients showing a MTV
TOT
≤ 9.5 ml as compared to those having MTV
TOT
> 9.5 ml (
p
< 0.0001). Similar results were obtained in a subgroup of 43 patients with advanced disease (stages III and IV).
Conclusions
Whole-body PET-based volumetric imaging parameters are able to predict outcome in NSCLC patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Gelsolin amyloidosis (AGel) is characterized by multiple systemic and ophthalmic features resulting from pathological tissue deposition of the gelsolin (GSN) protein. To date, no cure is available ...for the treatment of any form of AGel. More than ten single-point substitutions in the
gene are responsible for the occurrence of the disease and, among them, D187N/Y is the most widespread variant. These substitutions undergo an aberrant proteolytic cascade, producing aggregation-prone peptides of 5 and 8 kDa, containing the Gelsolin Amyloidogenic Core, spanning residues 182-192 (GAC
). Following a structure-based approach, we designed and synthesized three novel sequence-specific peptidomimetics (LB-5, LB-6, and LB-7) built on a piperidine-pyrrolidine unnatural amino acid. LB-5 and LB-6, but not LB-7, efficiently inhibit the aggregation of the GAC
amyloidogenic peptides at sub-stoichiometric concentrations. These peptidomimetics resulted also effective in vivo, in a
-based assay, in counteracting the proteotoxicity of aggregated GAC
. These data pave the way to a novel pharmacological strategy against AGel and also validate a toolbox exploitable in other amyloidogenic diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose The aim of the present study was to test whether the coefficient of variation (CoV) of 18F-FDG PET/CT images of metastatic lymph nodes and primary tumors may predict clinical outcome in ...patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods Fifty-eight NSCLC patients who had undergone 18F-FDG PET/CT at diagnosis were evaluated. SUVmax, SUVmean, CoV, MTV and TLG were determined in targeted lymph nodes and corresponding primary tumors along with Total MTV (MTVTOT) and Whole-Body TLG (TLGWB) of all malignant lesions. Univariate analysis was performed using Cox proportional hazards regression whereas the Kaplan–Meier method and log-rank tests were used for survival analysis. Results Fifty-eight metastatic lymph nodes were analyzed and average values of SUVmax, SUVmean, CoV, MTV and TLG were 11.89 ± 8.54, 4.85 ± 1.90, 0.37 ± 0.16, 46.16 ± 99.59 mL and 256.84 ± 548.27 g, respectively, whereas in primary tumors they were 11.92 ± 6.21, 5.47 ± 2.34, 0.36 ± 0.14, 48.03 ± 64.45 mL and 285.21 ± 397.95 g, respectively. At univariate analysis, overall survival (OS) was predicted by SUVmax (p = 0.0363), SUVmean (p = 0.0200) and CoV (p = 0.0139) of targeted lymph nodes as well as by CoV of primary tumors (p = 0.0173), MTVTOT (p = 0.0007), TLGWB (p = 0.0129) and stage (p = 0.0122). Using Kaplan–Meier analysis, OS was significantly better in patients with CoV of targeted lymph nodes ≤ 0.29 than those with CoV > 0.29 (p = 0.0147), meanwhile patients with CoV of primary tumors > 0.38 had a better prognosis compared to those with CoV ≤ 0.38 (p = 0.0137). Finally, we combined the CoV values of targeted lymph nodes and primary tumors in all possible arrangements and a statistically significant difference was found among the four survival curves (p = 0.0133). In particular, patients with CoV of targeted lymph nodes ≤ 0.29 and CoV of primary tumors > 0.38 had the best prognosis. Conclusions The CoV of targeted lymph nodes combined with the CoV of primary tumors can predict prognosis of NSCLC patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The chiral structure of antibiotic vancomycin (Van) was exploited as an innovative coordination sphere for the preparation of an IrCp* based hybrid catalysts. We found that Van is able to coordinate ...iridium (Ir(III)) and the complexation was demonstrated by several analytical techniques such as MALDI-TOF, UV, Circular dichroism (CD), Raman IR, and NMR. The hybrid system so obtained was employed in the Asymmetric Transfer Hydrogenation (ATH) of cyclic imines allowing to obtain a valuable 61%
(
) in the asymmetric reduction of quinaldine
. The catalytic system exhibited a saturation kinetics with a calculated efficiency of K
/K
= 0.688 h
mM
.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Poor colloidal stability of gold nanoparticles (AuNPs) in physiological environments remains one of the major limitations that contribute to their difficult translation from bench to clinic. For this ...reason, an active research field is the development of molecules able to hamper AuNPs aggregation tendency in physiological environments. In this context, synthetic peptides are gaining an increased interest as an alternative to the use of biomacromolecules and polymers, due to their easiness of synthesis and their profitable pharmacokinetic profile. In this work, we reported on the use of ultrashort peptides containing conformationally constrained amino acids (AAs) for the stabilization of AuNPs. A small library of non-natural self-assembled oligopeptides were synthesized and used to functionalize spherical AuNPs of 20 nm diameter,
the ligand exchange method. The aim was to investigate the role of the constrained AA, the anchor point (at C- or N-
) and the peptide length on their potential use as gold binding motif. Ultrashort Aib containing peptides were identified as effective tools for AuNPs colloidal stabilization. Furthermore, peptide coated AuNPs were found to be storable as powders without losing the stabilization properties once re-dispersed in water. Finally, the possibility to exploit the developed systems for binding proteins
molecular recognition was also evaluated using biotin as model.
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