Peptydy z węzłem cysteinowym jako inhibitory kallikreiny 13

• Autorzy: Jankowska Dżesika , Rejmak Wiktoria , Lesner Adam , Gruba Natalia

Identyfikatory

DOI

10.53584/wiadchem.2024.03.9

Warianty tytułu

EN

inhibitory cysteine peptides as kallikrein 13 inhibitors

• Języki publikacji: EN

Abstrakty

EN

Inhibitor cysteine knots (ICK) also known as "knottins," are cysteine-rich peptides typically composed of approximately 30 amino acids. These peptides exhibit a characteristic robust structure featuring three antiparallel β-sheets that are "knotted" together by three disulfide bonds. This structural motif confers stability to the protein, rendering it resistant to thermal denaturation and proteolysis. Consequently, inhibitor cysteine knots hold great promise as scaffolds for developing new peptide drugs. In this study, we present the synthesis and evaluation of six potential inhibitors targeting KLK13, utilizing the Ecballium elaterium trypsin II inhibitor (EETI-II) as the leading structure. The peptides were synthesized in solid-phase peptide synthesis with an automated peptide synthesizer. Subsequently, they were oxidized using iodine and then quenched with an anion exchange resin. Both linear and oxidized compounds were obtained and subjected to kinetic studies. The inhibitory activity against KLK13 was observed exclusively in the oxidized analogues of the synthesized compounds. Linear peptides exhibited lower affinity towards KLK13, highlighting the critical role of the disulfide bridge in the structure of the EETI-II analogues for inhibiting the enzyme activity.

Słowa kluczowe

EN

EETI-II analogs; competitive inhibition; kallikrein 13

PL

analogi EETI-II; inhibicja kompetycyjna; kallikreina 13

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Wiadomości Chemiczne
• Rocznik: 2024
• Tom: [Z] 78, 3-4
• Strony: 346--368
• Opis fizyczny: Bibliogr. 62 poz.,rys., tab., wykr.

Twórcy

autor

Jankowska Dżesika

• Wydział Chemii Uniwersytetu Gdańskiego, Ul. Wita Stwosza 63 80-308 Gdańsk

autor

Rejmak Wiktoria

• Wydział Chemii Uniwersytetu Gdańskiego, Ul. Wita Stwosza 63 80-308 Gdańsk

• https://orcid.org/0000-0002-2551-6869

autor

Lesner Adam

• Wydział Chemii Uniwersytetu Gdańskiego, Ul. Wita Stwosza 63 80-308 Gdańsk

• https://orcid.org/0000-0001-8335-3431

autor

Gruba Natalia

• Wydział Chemii Uniwersytetu Gdańskiego, Ul. Wita Stwosza 63 80-308 Gdańsk

• https://orcid.org/0000-0003-3281-9945

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