Synergistic screening of peptide-based biotechnological drug candidates for neurodegenerative diseases using yeast display and phage display

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buir.contributor.authorÖzçelik, Cemile Elif
buir.contributor.authorBeğli, Özge
buir.contributor.authorHınçer, Ahmet
buir.contributor.authorAhan, Recep Erdem
buir.contributor.authorOğuz, Oğuzhan
buir.contributor.authorKasırga, Talip Serkan
buir.contributor.authorŞeker, Urartu Özgür Şafak
buir.contributor.orcidHınçer, Ahmet|0000-0002-5151-6192
buir.contributor.orcidAhan, Recep Erdem|0000-0002-6061-9062
buir.contributor.orcidOğuz, Oğuzhan|0000-0003-3128-7334
buir.contributor.orcidKasırga, Talip Serkan|0000-0003-3510-5059
buir.contributor.orcidŞeker, Urartu Özgür Şafak|0000-0002-5272-1876
dc.citation.epage3621en_US
dc.citation.issueNumber19
dc.citation.spage3609
dc.citation.volumeNumber14
dc.contributor.authorÖzçelik, Cemile Elif
dc.contributor.authorBeğli, Özge
dc.contributor.authorHınçer, Ahmet
dc.contributor.authorAhan, Recep Erdem
dc.contributor.authorKesici, M. S.
dc.contributor.authorOğuz, Oğuzhan
dc.contributor.authorKasırga, Talip Serkan
dc.contributor.authorÖzçubukçu, S.
dc.contributor.authorŞeker, Urartu Özgür Şafak
dc.date.accessioned2024-03-11T08:34:18Z
dc.date.available2024-03-11T08:34:18Z
dc.date.issued2023-10-04
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)
dc.departmentAysel Sabuncu Brain Research Center (BAM)
dc.description.abstractPeptide therapeutics are robust and promising molecules for treating diverse disease conditions. These molecules can be developed from naturally occurring or mimicking native peptides, through rational design and peptide libraries. We developed a new platform for the rapid screening of the peptide therapeutics for disease targets. In the course of the study, we aimed to employ our platform to screen a new generation of peptide therapeutic candidates against aggregation-prone protein targets. Two peptide drug candidates were screened for protein aggregation-prone diseases, namely, Parkinson’s and Alzheimer’s diseases. Currently, there are several therapeutic applications that are only effective in masking or slowing down symptom development. Nonetheless, different approaches are being developed for inhibiting amyloid aggregation in the secondary nucleation phase, which is critical for amyloid fibril formation. Instead of targeting secondary nucleated protein structures, we tried to inhibit the aggregation of monomeric amyloid units as a novel approach for halting the disease condition. To achieve this, we combined yeast surface display and phage display library platforms. We expressed α-synuclein, amyloid β40, and amyloid β42 on the yeast surface, and we selected peptides by using phage display library. After iterative biopanning cycles optimized for yeast cells, several peptides were selected for interaction studies. All of the peptides have been used for in vitro characterization methods, which are quartz crystal microbalance-dissipation (QCM-D) measurement, atomic force microscopy (AFM) imaging, dot-blotting, and ThT assay, and some of them have yielded promising results in blocking fibrillization. The rest of the peptides, although, interacted with amyloid units which made them usable as a sensor molecule candidate. Therefore, peptides selected by yeast surface display and phage display library combination are good choice for diverse disease-prone molecule inhibition, particularly those inhibiting fibrillization. Additionally, these selected peptides can be used as drugs and sensors to detect diseases quickly and halt disease progression.
dc.description.provenanceMade available in DSpace on 2024-03-11T08:34:18Z (GMT). No. of bitstreams: 1 Synergistic_screening_of_peptide-based_biotechnological_drug_candidates_for_neurodegenerative_diseases_using_yeast_display_and_phage_display.pdf: 7438777 bytes, checksum: 74a8d6f87c5da226abcf39a0491724d3 (MD5) Previous issue date: 2023-10-04en
dc.identifier.doi10.1021/acschemneuro.3c00248
dc.identifier.issn19487193
dc.identifier.urihttps://hdl.handle.net/11693/114484
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.relation.isversionofhttps://dx.doi.org/10.1021/acschemneuro.3c00248
dc.source.titleACS Chemical Neuroscience
dc.subjectYeast surface display
dc.subjectPhage display library
dc.subjectNeurodegenerative disease
dc.subjectPeptide-based drug discovery
dc.titleSynergistic screening of peptide-based biotechnological drug candidates for neurodegenerative diseases using yeast display and phage display
dc.typeArticle

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