Naslov
Esterase-inspired short catalytic peptides with tunable activity

Autori
Janković, Patrizia ; Todorovski, Toni ; Pina, Ana Sofia ; Kalafatovic, Daniela​

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
11th Austrian Peptide Symposium

Mjesto i datum
Beč, Austrija, 01-01.12.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
peptides, catalytic, cyclic, minimalistic

Sažetak
Short catalytic peptides are tunable, low-cost biomolecules able to catalyze chemical reactions such as ester hydrolysis1. The main drawback is their low catalytic efficiency attributed to the lack of well-defined tridimensional structures characteristic for enzymes. Peptide self-assembly offers the possibility to obtain nanostructures with a higher degree of order leading to improved catalytic efficiency2. Alternatively, the cyclization of linear peptides restrains their conformational freedom, stabilizing the active site. Our aim is to design short catalytic linear and cyclic peptides to assess whether the enhanced rigidity obtained by cyclization improves their catalytic efficiency. The design of the sequences was inspired by active sites found in hydrolases acting on ester bonds (EC 3.1.) and it was based on the selection of a fragment containing the triad, from the primary sequence of the active site, retaining its chemical environment (Figure 1). Selected sequences from the 1-alkyl-2- acetylglycerophosphocholine esterase and protein- glutamate methylesterases (CheD and CheB) were synthesized using solid-phase peptide synthesis (SPPS) approach. The cyclization was achieved by three different methods (head-to-side chain, disulfide bridge formation and side chain-to-side chain) depending on the sequence composition. The peptides were purified using semipreparative-HPLC and characterized by LC-MS and analytical HPLC. The catalytic activities of the linear and cyclic peptides were evaluated using the 4-nitrophenyl acetate (p-NPA) colorimetric test and the obtained results will be described. Additionally, analogues of cysteine-containing peptides were designed and synthesized. The oxidation kinetics and the effect of thiol groups on catalytic activity were investigated. A successful outcome of this project will contribute to a better understanding of the relationship between short peptide sequences and their catalytic activity applicable to peptides with esterase activity.

Izvorni jezik
Engleski

Znanstvena područja
Interdisciplinarne prirodne znanosti, Biotehnologija, Interdisciplinarne biotehničke znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA