التفاصيل البيبلوغرافية
| العنوان: |
Screening and Analysis of Inhibitors against Staphylococcal Superantigen-like Protein 7 ; Sållning och analys av inhibitorer mot stafylokock superantigen-like protein 7 |
| المؤلفون: |
Andersin, Micaela |
| المساهمون: |
Åbo Akademi, Fakulteten för naturvetenskaper och teknik, Biokemi |
| سنة النشر: |
2024 |
| المجموعة: |
Doria (National Library of Finland / |
| مصطلحات موضوعية: |
Staphylococcus aureus, staphylococcal superantigen-like protein 7, structure-based drug design, enzyme-linked immunosorbent assay, screening analysis, molecular dynamics, bacteria, MRSA, staphylococci, prevention, proteins, peptides, drug design, sållning, molekyldynamik, bakterier, stafylokocker, proteiner, peptider, läkemedelsdesign, seulonta, molekyylidynamiikka, bakteerit, stafylokokit, ehkäisy, proteiinit, peptidit, lääkesuunnittelu, 1182 Biokemi, cell- och molekylbiologi |
| الوصف: |
Staphylococcus aureus (S. Aureus) can infect, colonize and survive in its host, utilizing 40 immune evasion proteins found up to date. By doing so it can cause a wide range of diseases including skin infections, sepsis or endocarditis. Furthermore, strains of S. aureus have developed a concerning amount of antibiotic resistance, presenting threats against human health today. Staphylococcal superantigen-like protein 7 (SSL7) is a bifunctional immune evading protein secreted by S. aureus. It can inhibit two parts of the immune response by binding to human immunoglobulin A (IgA) and complement component 5 (C5). This bifunctionality and the antibiotic resistance of S. aureus makes SSL7 an attractive drug target to fight against infections caused by the bacterium. SSL7 binds IgA by its oligonucleotide binding (OB) site, preventing it from recognizing S. aureus cells. This way IgA will not be able to bind to S. aureus and further be recognized by the IgA fragment crystallizable receptor. The receptor recognizes IgA-pathogen complexes, such as S. aureus–IgA complexes, and promotes their elimination. Additionally, by binding to C5, SSL7 inhibits its cleavage by C5 convertase to C5a and C5b. This halts the downstream pathway responsible for S. aureus elimination, as C5a is responsible for activation of neutrophils. Utilizing structure-based drug design, peptides and macrocycles were screened against IgA and C5 binding sites of SSL7, to find ones that show potential inhibitory effect against the protein. Methods such as molecular docking, binding energy calculations and molecular dynamics simulation were used to rank these ligands and analyze their estimated binding properties in the SSL7 binding sites. To validate the predicted binding of top ranked hits against SSL7, the protein was expressed in Escherichia coli to further study the ligand binding in an enzyme-linked immunosorbent assay. Seven peptides and nine macrocycles were predicted to have promising binding affinity towards SSL7. The peptides were predicted to ... |
| نوع الوثيقة: |
thesis |
| وصف الملف: |
true |
| اللغة: |
Swedish |
| العلاقة: |
https://www.doria.fi/handle/10024/188825Test; URN:NBN:fi-fe2024030710355 |
| الإتاحة: |
https://www.doria.fi/handle/10024/188825Test |
| حقوق: |
This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited. ; Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden. ; Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty. ; sv=Avhandlingen kan enbart läsas vid Boktornet och Academillbiblioteket.|fi=Kokoteksti on luettavissa vain Kirjatornissa ja Academill-kirjastossa.|en=Full-text can be read only at the Book Tower and Academill Library.| |
| رقم الانضمام: |
edsbas.94F9A74E |
| قاعدة البيانات: |
BASE |
