Tailoring short self-assembling peptides into biocompatible gelators
| dc.contributor.author | Datta, Debika | |
| dc.date.accessioned | 2020-08-05T10:10:11Z | |
| dc.date.accessioned | 2023-10-19T11:05:00Z | |
| dc.date.available | 2020-08-05T10:10:11Z | |
| dc.date.available | 2023-10-19T11:05:00Z | |
| dc.date.issued | 2019 | |
| dc.description | Supervisors: Nitin Chaudhary and Vibin Ramakrishnan | en_US |
| dc.description.abstract | The thesis largely focuses on the self-assembly of designed amyloidogenic and fatty-acylated peptides and their potential applications in healthcare. The short amyloidogenic-stretch of β-amyloid, Aβ16-22 (Ac-KLVFFAE-am), is a useful model peptide to study the aspects of β-amyloid fibril formation. Herein, the self-assembly was investigated by incorporating β-turn-inducing motifs (Asn-Gly, DPro-Gly, and Aib-DPro), in the Ac-KLVXZAE-am chains, where X and Z are the aromatic amino acids, Phe, Tyr, or Trp. The peptides harboring β-turn-inducing motifs aggregate rapidly, cause substantial enhancements in thioflavin T (ThT) fluorescence compared to the controls, the β-turn motif-lacking peptides. The thesis also discusses the theoretical results obtained from molecular dynamics simulation of the turn-containing peptides, giving insights into the type of turn formed. A follow-up investigation into the amyloidogenic propensity showed that the aromatic analogue AβFY (Ac-KLVFYAE-am) and Aβ16-22 repeats (specifically the ones having Phe-Phe or Phe-Tyr aromatic cassette in their sequence) connected through Asn-Gly, Aib-DPro, and DPro-Gly forms self-supporting soft gels at concentrations ≥2 mM, even though the end-capped parent peptide does not form hydrogel up to 20 mM (1.8% w/w) concentration in 10% HFIP. The study delves into the characterization and possible applications of the hydrogel. The hydrogels made up of amyloid-like fibers possess distinct elastic properties. The gel is shown to support the growth of rat pancreatic cells (RIN-5F), human embryonic kidney cells (HEK-293), baby hamster kidney cells (BHK-21), and human neuroblastoma cells (IMR-32). The results include the doxorubicin release assay showing its potential as a drug-delivery vehicle, the thermal/mechano response of the gels, as well as the gelation at the acidic pH. To gain insights into the folded conformation, investigation of the β-turn-supporting motifs was also carried out using proton NMR spectroscopy (1H, TOCSY and NOESY). Individual amino acids or pairs of amino acids such as AA, KK, LL, VV, Aromatic-Aromatic, EE, could be unambiguously identified. The data, was interpreted using the chemical shift indices and indicated turn formation. | en_US |
| dc.identifier.other | ROLL NO.136106018 | |
| dc.identifier.uri | https://gyan.iitg.ac.in/handle/123456789/1510 | |
| dc.language.iso | en | en_US |
| dc.relation.ispartofseries | TH-2177; | |
| dc.subject | BIOSCIENCES AND BIOENGINEERING | en_US |
| dc.title | Tailoring short self-assembling peptides into biocompatible gelators | en_US |
| dc.type | Thesis | en_US |
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