Publications

Authors:

Grifagni, Deborah; Lenci, Elena; De Santis, Alessia; Orsetti, Andrea; Barracchia, CARLO GIORGIO; Tedesco, Filomena; Bellini Puglielli, Raffaele; Lucarelli, Francesca; Lauriola, Angela; Assfalg, Michael; Cantini, Francesca; Calderone, Vito; Guardavaccaro, Daniele; Trabocchi, Andrea; D’Onofrio, Mariapina; Simone Ciofi-Baffoni, And

Title:

Development of a GC-376 Based Peptidomimetic PROTAC as a Degrader of 3‐Chymotrypsin-like Protease of SARS-CoV‐2

Year:

2024

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

A Stampa

Referee:

Sì

Name of journal:

ACS MEDICINAL CHEMISTRY LETTERS

ISSN of journal:

1948-5875

N° Volume:

15

Number or Folder:

2

Page numbers:

250-257

Keyword:

3-Chymotrypsin-like protease; Bioconjugate chemistry; COVID-19; Infectious diseases; Peptidomimetics; PROTAC

Short description of contents:

We have applied a proteolysis targeting chimera (PROTAC) technology to obtain a peptidomimetic molecule able to trigger the degradation of SARS-CoV-2 3-chymotrypsin-like protease (3CLPro). The PROTAC molecule was designed by conjugating a GC-376 based dipeptidyl 3CLPro ligand to a pomalidomide moiety through a piperazine−piperidine linker. NMR and crystallographic data complemented with enzymatic and cellular studies showed that (i) the dipeptidyl moiety of PROTAC binds to the active site of the dimeric state of SARS-CoV-2 3CLPro forming a reversible covalent bond with the sulfur atom of catalytic Cys145, (ii) the linker and the pomalidomide cereblon-ligand of PROTAC protrude from the protein, displaying a high degree of flexibility and no interactions with other regions of the protein, and (iii) PROTAC reduces the protein levels of SARS-CoV-2 3CLPro in cultured

Product ID:

137435

Handle IRIS:

11562/1118190

Last Modified:

March 29, 2024

Bibliographic citation:

Grifagni, Deborah; Lenci, Elena; De Santis, Alessia; Orsetti, Andrea; Barracchia, CARLO GIORGIO; Tedesco, Filomena; Bellini Puglielli, Raffaele; Lucarelli, Francesca; Lauriola, Angela; Assfalg, Michael; Cantini, Francesca; Calderone, Vito; Guardavaccaro, Daniele; Trabocchi, Andrea; D’Onofrio, Mariapina; Simone Ciofi-Baffoni, And, Development of a GC-376 Based Peptidomimetic PROTAC as a Degrader of 3‐Chymotrypsin-like Protease of SARS-CoV‐2 «ACS MEDICINAL CHEMISTRY LETTERS» , vol. 15 , n. 2 , 2024 , pp. 250-257

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo