Logo del repository
  1. Home
 
Opzioni

Small hydroxyethylene-based peptidomimetics inhibiting both HIV-1 and C. albicans aspartic protease

TOSSI, ALESSANDRO
•
BENEDETTI, FABIO
•
NORBEDO, STEFANO
altro
ROMEO, DOMENICO
2003
  • journal article

Periodico
BIOORGANIC & MEDICINAL CHEMISTRY
Abstract
We have extended a highly flexible method for rapidly assembling aspartic protease inhibitors to produce symmetric and asymmetric monohydroxyethylene peptidomimetics. This method is based on the prior synthesis of the central non-cleavable peptide- bond isostere [NH2–P1cP10–NH2; c=hydroxyethylene isostere, HNCH(Bz)CHOHCH2CH(Bz)NH], with the possibility of accurately controlling its stereochemistry (S,S,S or S,R,S), and subsequently adding appropriate flanking units, chosen from commercially available amino acids, aromatic carboxylic acids, or phenoxyacetic acid (Poa) derivatives. The method was used to make asymmetric inhibitors of general formula Kyn-Xaa-PhecPhe-dmPoa, (Kyn=kynurenic acid, Xaa=Val, Thr or d-thienylglycine, Mr=716–754) and symmetric inhibitors of formula xPoa-PhecPhe-xPoa (xPoa=Poa or dimethyl-, hydroxy-, formyl- or acetyl- Poa, Mr=553–609), with logPo/w values ranging from 4.1 to 7.6. Inhibition of HIV-PR did not depend on the stereochemistry of the hydroxyl group, while it depended markedly on the substituents present on the Poa residues, with dmPoa being preferred over Poa or its more hydrophilic derivatives. Conversely, inhibition of Candida albicans Sap2 was higher for the S,S,S epimers, and Poa or its hydrophilic derivatives were preferred over dmPoa.
DOI
10.1016/j.bmc.2003.08.004
WOS
WOS:000186134200004
Archivio
http://hdl.handle.net/11368/1690091
info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-0141888592
Diritti
metadata only access
Soggetti
  • Protease Inhibitor

  • SAP

  • Hydroxyethylene Isost...

  • HIV protease

  • Peptidomimetics

Scopus© citazioni
31
Data di acquisizione
Jun 14, 2022
Vedi dettagli
Web of Science© citazioni
29
Data di acquisizione
Feb 26, 2024
Visualizzazioni
2
Data di acquisizione
Apr 19, 2024
Vedi dettagli
google-scholar
Get Involved!
  • Source Code
  • Documentation
  • Slack Channel
Make it your own

DSpace-CRIS can be extensively configured to meet your needs. Decide which information need to be collected and available with fine-grained security. Start updating the theme to match your nstitution's web identity.

Need professional help?

The original creators of DSpace-CRIS at 4Science can take your project to the next level, get in touch!

Realizzato con Software DSpace-CRIS - Estensione mantenuta e ottimizzata da 4Science

  • Impostazioni dei cookie
  • Informativa sulla privacy
  • Accordo con l'utente finale
  • Invia il tuo Feedback