Bellavita, Rosa
DESIGN & SYNTHESIS OF PEPTIDOMIMETICS AS TOOLBOX TO PROBE EMERGING ANTIMICROBIAL AND ANTICANCER STRATEGIES.
[Tesi di dottorato]
| Item Type: |
Tesi di dottorato
|
| Resource language: |
English |
| Title: |
DESIGN & SYNTHESIS OF PEPTIDOMIMETICS AS TOOLBOX TO PROBE EMERGING ANTIMICROBIAL AND ANTICANCER STRATEGIES |
| Creators: |
| Creators | Email |
|---|
| Bellavita, Rosa | rosa.bellavita@unina.it |
|
| Number of Pages: |
112 |
| Institution: |
Università degli Studi di Napoli Federico II |
| Department: |
Farmacia |
| Dottorato: |
Scienza del farmaco |
| Ciclo di dottorato: |
33 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| D'Auria, Maria Valeria | madauria@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Grieco, Paolo | UNSPECIFIED |
|
| Number of Pages: |
112 |
| Keywords: |
temporin L, beta-catenin, cyclic peptides |
| Settori scientifico-disciplinari del MIUR: |
Area 03 - Scienze chimiche > CHIM/08 - Chimica farmaceutica |
[error in script]
[error in script]
| Date Deposited: |
24 Feb 2021 08:59 |
| Last Modified: |
07 Jun 2023 10:18 |
| URI: |
http://www.fedoa.unina.it/id/eprint/14121 |
Collection description
Infections caused by ESKAPE pathogens are a huge challenge in both human and veterinary medicine. Among the antimicrobial peptides (AMPs), temporins represent encouraging candidates since they act through a different mode of action from conventional antibiotics. Despite the strong antimicrobial activity, the native Temporin L has not considered an efficacious alternative due to its cytotoxicity. In this scenario, our efforts have been addressed to the improvement of drug-like features of some Temporin L analogues, applying several synthetic approaches spanning from local modification and conformational constraints. Specifically, we performed local modifications consisting of the incorporation of D-amino acids or "decorated prolines" featured by appropriate functional groups (polar-, positively charged-, aliphatic- and aromatic groups) and lipidation strategy in order to improve antimicrobial activity and to preserve low cytotoxicity. In addition, we probed the correlation between alpha-helix secondary structure and antimicrobial activity using different side-chain to side-chain cyclization strategies. In particular, lactamization, the formation of disulfide bridge between cysteines, triazole formation by CuAAC click chemistry reaction, and ring closing metathesis were used to stabilize alpha-helical conformation and to increase the biological activity. Thanks to the application of these several synthetic strategies, we discovered novel Temporin L analogues with a high therapeutic index that have shown characteristics desired to be good candidates in the development of novel antimicrobial agents for topical applications.
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