Naslov
Esterase Sequence Composition Patters As Inspiration For The Design Of Short Catalytic Peptides

Autori
Kalafatovic, Daniela ; Janković, Patrizia ; Babić, Marko ; Pina, Ana Sofia ; Mauša, Goran

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
Chemistry and Biology of Peptides Gordon Research Conference

Mjesto i datum
Oxnard, California, USA, 30.10.2022. - 04.11.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
catalytic peptides ; ester hydrolysis ; catalytic triad

Sažetak
Ester hydrolysis is of wide biomedical interest, spanning from the green synthesis of pharmaceuticals to biomaterials' development. Existing peptide-based catalysts exhibit low catalytic efficiency compared to natural enzymes, due to the conformational heterogeneity of peptides. Moreover, there is lack of understanding of the correlation between the primary sequence and catalytic function. First, we statistically analyzed 22 EC 3.1 hydrolases with known catalytic triads, characterized by unique mechanisms. We extended this analysis to 974 homologues to verify the identified microenvironment motifs. The aim was to identify patterns at the sequence level that will better inform the creation of short peptides containing important information for catalysis, based on the catalytic triad, oxyanion holes and the triad residues microenvironments. The results showed highly conserved catalytic sites with distinct positional patterns, chemical microenvironments that favor catalysis and revealed variations in catalytic site composition that could be useful for the design of minimalistic catalysts. Next, linear and cyclic peptides were synthesized and their ability to catalyze pNPA hydrolysis was tested. The control over catalytic performance of peptides was achieved through modifications at the sequence level and by varying the chemical environment.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Računarstvo, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA