Naslov
Hydrolase-inspired design of short catalytic linear and cyclic peptides

Autori
Janković, Patrizia ; Todorovski, Toni ; Kalafatovic, Daniela

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

Skup
36th European and 12th International Peptide Symposium

Mjesto i datum
Barcelona, Španjolska; Sitges, Španjolska, 28.08.2022. - 02.09.2022

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 hydrolysis 1 . 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 efficiency. 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). Three sequences (SGNYDYLHGE, CTLGLGSHCGG, and GGESTGHTGAGNDK) obtained from the 1-alkyl-2 acetylglycerophosphocholine esterase and protein- glutamate methylesterases (CheD and CheB), respectively, 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, while their ability to self- assemble and form possible nanostructures was assessed through FTIR, CD and fluorescence spectroscopy analyses. 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. 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
Kemija, Interdisciplinarne prirodne znanosti, Biotehnologija, Interdisciplinarne biotehničke znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA