Accurate diagnosis of the preclinical stages of Alzheimer's disease (AD), by means of biomarker early detection, is considered crucial for therapeutic advancements. Current AD diagnosis relies on the combi- natorial use of biomarkers detection, derived from cerebrospinal fluid (CSF), with advanced molecular imaging and cognitive assessment tools [1]. However, the invasiveness and the difficult access to rou- tine diagnosis, due to high costs of these tools, represent some chal- lenges that need to be overcome. Low-cost and non-invasive alternatives, such as plasma, saliva, or urine biomarkers, could be a valid substitute in AD screening and diagnosis. Nanomaterial-based biosensors development for recognition of AD biomarkers, such as amyloid beta Aβ(1–40) and the more toxic form Aβ (1–42), could pave the way for early diagnosis of AD. In this scenario, KLVFF (H2N-Lys-Leu-Val-Phe-Phe-COOH, Aβ (16–20)), a peptide fragment deputed to interact with the homologous region of full-length Aβ(1– 40) or Aβ (1–42), was selected as molecular recognition element of the selected Aβ biomarkers. KLVFF conjugates were grafted to gra- phene oxide (GO) chosen as nanomaterials-based sensing layer. To this aim, two different approaches were exploited. In one case, the GO surface was decorated, using the thin film hydration method [2], with amphiphilic cyclodextrin SC16OH nanovesicles entangling the hydrophobic peptide Ada-(PEG)4-KLVFF. In the other approach the peptide H2N-(PEG)4-KLVFF was covalently conjugated with GO using an optimized EDC/NHS coupling protocol, where the activated carboxyl groups of GO surface are allowed to react with the N-terminal amino group of the peptide conjugate. Functionalized nanomaterials obtained by both the investigated approaches were characterized by Fourier-transform infrared (FT-IR), X-ray photoelec- tron spectroscopy (XPS) and scanning electron microscopy (SEM), in order to observe chemical and morphological changes due to functio- nalization processes. The new nanomaterials, that allow to integrate the electrical properties of GO and the recognition capabilities of KLVFF, could have enormous potential as a multifunctional platform for biomedical applications as biosensing layers for AD's biomarker detection.

37th European Peptide Symposium-14th International Peptide Symposium

Rita Turnaturi;Giuseppina Sabatino;Giuseppe Di Natale;Giuseppe Nocito;Viviana Scuderi;Simona Filice;Antonino Mazzaglia;Silvia Scalese;Giuseppe Pappalardo
2024

Abstract

Accurate diagnosis of the preclinical stages of Alzheimer's disease (AD), by means of biomarker early detection, is considered crucial for therapeutic advancements. Current AD diagnosis relies on the combi- natorial use of biomarkers detection, derived from cerebrospinal fluid (CSF), with advanced molecular imaging and cognitive assessment tools [1]. However, the invasiveness and the difficult access to rou- tine diagnosis, due to high costs of these tools, represent some chal- lenges that need to be overcome. Low-cost and non-invasive alternatives, such as plasma, saliva, or urine biomarkers, could be a valid substitute in AD screening and diagnosis. Nanomaterial-based biosensors development for recognition of AD biomarkers, such as amyloid beta Aβ(1–40) and the more toxic form Aβ (1–42), could pave the way for early diagnosis of AD. In this scenario, KLVFF (H2N-Lys-Leu-Val-Phe-Phe-COOH, Aβ (16–20)), a peptide fragment deputed to interact with the homologous region of full-length Aβ(1– 40) or Aβ (1–42), was selected as molecular recognition element of the selected Aβ biomarkers. KLVFF conjugates were grafted to gra- phene oxide (GO) chosen as nanomaterials-based sensing layer. To this aim, two different approaches were exploited. In one case, the GO surface was decorated, using the thin film hydration method [2], with amphiphilic cyclodextrin SC16OH nanovesicles entangling the hydrophobic peptide Ada-(PEG)4-KLVFF. In the other approach the peptide H2N-(PEG)4-KLVFF was covalently conjugated with GO using an optimized EDC/NHS coupling protocol, where the activated carboxyl groups of GO surface are allowed to react with the N-terminal amino group of the peptide conjugate. Functionalized nanomaterials obtained by both the investigated approaches were characterized by Fourier-transform infrared (FT-IR), X-ray photoelec- tron spectroscopy (XPS) and scanning electron microscopy (SEM), in order to observe chemical and morphological changes due to functio- nalization processes. The new nanomaterials, that allow to integrate the electrical properties of GO and the recognition capabilities of KLVFF, could have enormous potential as a multifunctional platform for biomedical applications as biosensing layers for AD's biomarker detection.
2024
Istituto di Cristallografia - IC - Sede Secondaria Catania
amyloid
neurodegeneration
biosensor
graphene oxide
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/516469
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