Innovative antimicrobial textiles based on natural fibers functionalized with peptaibiotics.

The need to develop new materials for a variety of applications is greatly promoting academic and industrial research. In this thesis work antimicrobial textiles were prepared. To contribute to this topic, we started a research program that heavily relies on our expertise in the field of antibacterial peptides. Among the many polymeric materials available, cellulose fibers are particularly attractive, being naturally occurring, and easy to functionalize. Peptides and dendrimers were immobilized, as antimicrobial agent, onto cotton fabrics. Preparation of immobilized peptide-cotton materials was obtained using different innovative synthetic methods. Characterization analysis by FT-IR, XPS, UV-Vis, TGA and EPR was also performed for qualitative and quantitative determination of cotton functionalization. Moreover, enzymatic degradation was carried out allowing the application of NMR spectroscopy in solution. Antimicrobial activity of samples were tested against Staphylococcus aureus (Gram positive bacteria) and Escherichia coli (Gram negative bacteria). Promising results were obtained against the Gram positive strain, while only few samples show good activity against Gram negative bacteria

Covalent Graft of Lipopeptides and Peptide Dendrimers to Cellulose Fibers

Introduction: Bacterial proliferation in health environments may lead to the development of specific pathologies, but can be highly dangerous under particular conditions, such as during chemotherapy. To limit the spread of infections, it is helpful to use gauzes and clothing containing antibacterial agents. As cotton tissues are widespread in health care environments, in this contribution we report the preparation of cellulose fibers characterized by the covalent attachment of lipopeptides as possible antimicrobial agents. Aim: To covalently link peptides to cotton samples and characterize them. Peptides are expected to preserve the features of the fabrics even after repeated washing and use. Peptides are well tolerated by the human body and do not induce resistance in bacteria. Materials and Methods: A commercially available cotton tissue (specific weight of 150 g/m2, 30 Tex yarn fineness, fabric density of 270/230 threads/10 cm in the warp and weft) was washed with alkali and bleached and died. A piece of this tissue was accurately weighed, washed with methanol (MeOH) and N,N-dimethylformamide (DMF), and air-dried. Upon incubation with epibromohydrin, followed by treatment with Fmoc-NH-CH2CH2-NH2 and Fmoc removal, the peptides were synthesized by incorporating one amino acid at a time, beginning with the formation of an amide bond with the free NH2 of 1,2\u2013diaminoethane. We also linked to the fibers a few peptide dendrimers, because the mechanism of action of these peptides often requires the formation of clusters. We prepared and characterized seven peptide-cotton samples. Results: The new peptide-cotton conjugates were characterized by means of FT-IR spectroscopy and X-ray Photoelectron Spectroscopy (XPS). This latter technique allows for discriminating among different amino acids and thus different peptide-cotton samples. Some samples maintain a pretty good whiteness degree even after peptide functionalization. Interestingly, these samples also display encouraging activities against a Gram positive strain. Conclusions: Potentially antimicrobial lipopeptides can be covalently linked to cotton fabrics, step-by-step. It is also possible to build on the cotton Lys-based dendrimers. XPS is a useful technique to discriminate among different types of nitrogen. Two samples displaying some antibacterial potency did also preserve their whiteness index

Copper(II) Lysinate and Pseudoproline Assistance in the Convergent Synthesis of the GLP-1 Receptor Agonists Liraglutide and Semaglutide

A growing interest in peptides as active pharmaceutical ingredients (APIs) requires the development of efficient strategies for their preparation. This is particularly challenging in the case of long peptides with a strong tendency for aggregation and folding. Here, we describe the pseudoproline-assisted convergent synthesis of GLP-1 receptor agonist lipopeptides liraglutide and semaglutide, which involves the stepwise condensation of three fragments in the solid phase. The insertion of a pseudoproline residue at the site of fragment coupling prevents aggregation and allows obtaining these peptides with excellent purity and high yield. In addition, for the synthesis of lipidated side chains, we developed a novel approach that involves copper(II) lysinate intermediates and can be particularly suitable for the industrial preparation of both liraglutide and semaglutide and other peptides with a similar branched structure.A growing interest in peptides as active pharmaceutical ingredients (APIs) requires the development of efficient strategies for their preparation. This is particularly challenging in the case of long peptides with a strong tendency for aggregation and folding. Here, we describe the pseudoproline-assisted convergent synthesis of GLP-1 receptor agonist lipopeptides liraglutide and semaglutide, which involves the stepwise condensation of three fragments in the solid phase. The insertion of a pseudoproline residue at the site of fragment coupling prevents aggregation and allows obtaining these peptides with excellent purity and high yield. In addition, for the synthesis of lipidated side chains, we developed a novel approach that involves copper(II) lysinate intermediates and can be particularly suitable for the industrial preparation of both liraglutide and semaglutide and other peptides with a similar branched structure

Covalent Graft of Lipopeptides and Peptide Dendrimers to Cellulose Fibers

Introduction: Bacterial proliferation in health environments may lead to the development of specific pathologies, but can be highly dangerous under particular conditions, such as during chemotherapy. To limit the spread of infections, it is helpful to use gauzes and clothing containing antibacterial agents. As cotton tissues are widespread in health care environments, in this contribution we report the preparation of cellulose fibers characterized by the covalent attachment of lipopeptides as possible antimicrobial agents. Aim: To covalently link peptides to cotton samples and characterize them. Peptides are expected to preserve the features of the fabrics even after repeated washing and use. Peptides are well tolerated by the human body and do not induce resistance in bacteria. Materials and Methods: A commercially available cotton tissue (specific weight of 150 g/m2, 30 Tex yarn fineness, fabric density of 270/230 threads/10 cm in the warp and weft) was washed with alkali and bleached and died. A piece of this tissue was accurately weighed, washed with methanol (MeOH) and N,N-dimethylformamide (DMF), and air-dried. Upon incubation with epibromohydrin, followed by treatment with Fmoc-NH-CH2CH2-NH2 and Fmoc removal, the peptides were synthesized by incorporating one amino acid at a time, beginning with the formation of an amide bond with the free NH2 of 1,2–diaminoethane. We also linked to the fibers a few peptide dendrimers, because the mechanism of action of these peptides often requires the formation of clusters. We prepared and characterized seven peptide-cotton samples. Results: The new peptide-cotton conjugates were characterized by means of FT-IR spectroscopy and X-ray Photoelectron Spectroscopy (XPS). This latter technique allows for discriminating among different amino acids and thus different peptide-cotton samples. Some samples maintain a pretty good whiteness degree even after peptide functionalization. Interestingly, these samples also display encouraging activities against a Gram positive strain. Conclusions: Potentially antimicrobial lipopeptides can be covalently linked to cotton fabrics, step-by-step. It is also possible to build on the cotton Lys-based dendrimers. XPS is a useful technique to discriminate among different types of nitrogen. Two samples displaying some antibacterial potency did also preserve their whiteness index

Innovative antimicrobial textiles based on natural fibers functionalized with peptaibiotics.

The need to develop new materials for a variety of applications is greatly promoting academic and industrial research. In this thesis work antimicrobial textiles were prepared. To contribute to this topic, we started a research program that heavily relies on our expertise in the field of antibacterial peptides. Among the many polymeric materials available, cellulose fibers are particularly attractive, being naturally occurring, and easy to functionalize. Peptides and dendrimers were immobilized, as antimicrobial agent, onto cotton fabrics. Preparation of immobilized peptide-cotton materials was obtained using different innovative synthetic methods. Characterization analysis by FT-IR, XPS, UV-Vis, TGA and EPR was also performed for qualitative and quantitative determination of cotton functionalization. Moreover, enzymatic degradation was carried out allowing the application of NMR spectroscopy in solution. Antimicrobial activity of samples were tested against Staphylococcus aureus (Gram positive bacteria) and Escherichia coli (Gram negative bacteria). Promising results were obtained against the Gram positive strain, while only few samples show good activity against Gram negative bacteria.La necessità di sviluppare nuovi materiali per una varietà di applicazioni sta interessando fortemente la ricerca accademica e industriale. In questo lavoro di tesi sono stati preparati dei tessuti antimicrobici. Per contribuire a questo argomento, abbiamo avviato un programma di ricerca che si basa sulla nostra esperienza nel campo dei peptidi antibatterici. Peptidi e dendrimeri sono stati immobilizzati, come agenti antimicrobici, su tessuti. Tra i molti materiali polimerici disponibili, le fibre di cellulosa sono particolarmente attraenti, essendo esse presenti in natura e facile da funzionalizzare. Caratterizzazioni FT-IR, XPS, UV-Vis, TGA e EPR sono state effettuate per la determinazione qualitativa e quantitativa della funzionalizzazione del cotone. Inoltre, la degradazione enzimatica ha consentito l'applicazione della spettroscopia 1H-NMR in soluzione. L'attività antimicrobica dei campioni è stata testata contro lo Staphylococcus aureus (batterio Gram-positivo) e l’Escherichia coli (batterio Gram-negativo). Risultati promettenti sono stati ottenuti contro i batteri Gram-positivi, mentre solo pochi campioni hanno mostrato una buona attività contro i batteri Gram-negativi.

Cotton functionalized with peptides: characterization and synthetic methods

Three approaches for the chemical ligation of peptides to cotton fibers are described and compared. This investigation was encouraged by the need to create peptide-decorated natural textiles, furnished with useful properties (e.g. antimicrobial activity). IR absorption spectroscopy is proved to be an easy and fast method to check the covalent anchorage of a peptide to cotton, whereas for a quantitative determination, a UV absorption method was employed. We also analyzed the usefulness of electron paramagnetic resonance spectroscopy to characterize our peptide-cotton conjugates

The Power of EPR Techniques in Investigating Functionalization and Penetration into Fibers of Cotton-Bound Antimicrobial Peptides

Abstract The development of protective and safe textiles is of fundamental importance for defending the human body from bacterial infections. To this aim, garments are often functionalized with antibacterial agents. We recently started a program aimed at covalently linking antimicrobial peptides to cotton tissues. To optimize the process of binding, it is necessary to know the degree of functionalization and how deeply peptides penetrate into the cotton fiber. Here, we present a spin-label electron paramagnetic resonance (EPR) approach for obtaining data on the peptide incorporation into the fibers. The approach is based on the line broadening in conventional EPR and on the signal decays in electron spin echo spectroscopy that is a pulsed version of EPR

Thermal Crosstalk Effects in a Silicon Photonics Neuromorphic Network

We propose a methodology to include thermal crosstalk effects in the modeling of neuromorphic photonic circuits. Through component-level simulations of device building blocks and thermal analysis, we are able to successfully account for thermal effects, as shown by a comparison with experimental measurements of a 3×3 programmable optical circuit

Innovative chemical synthesis and conformational hints on the lipopeptide liraglutide

Liraglutide is a new generation lipopeptide drug used for the treatment of type II diabetes. In this work, we describe new approaches for its preparation fully by chemical methods. The key step of these strategies is the synthesis in solution of the Lys/-Glu building block, Fmoc-Lys-(Pal--Glu-OtBu)-OH, in which Lys and Glu residues are linked through their side chains and -Glu is N-palmitoylated. This dipeptide derivative is then inserted into the peptide sequence on solid phase. As liraglutide is obtained with great purity and high yield, our approach can be particularly attractive for an industrial production. We also report here the results of a circular dichroism conformational analysis in a membrane mimetic environment that offers new insights into the mechanism of action of liraglutide