Application of the Ugi reaction with multiple amino acid-derived components: synthesis and conformational evaluation of piperazine-based minimalist peptidomimetics.

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Stucchi M., Cairati S., Cetin-Atalay R., Christodoulou M. S., Grazioso G., Pescitelli G., ...Daha Fazla

Organic & biomolecular chemistry, cilt.13, sa.17, ss.4993-5005, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 13 Sayı: 17
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1039/c5ob00218d
  • Dergi Adı: Organic & biomolecular chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.4993-5005
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

The concurrent employment of alpha-amino acid-derived chiral components such as aldehydes and alpha-iso-cyanoacetates, in a sequential Ugi reaction/cyclization two-step strategy, opens the door to the synthesis of three structurally distinct piperazine-based scaffolds, characterized by the presence of L-Ala and/or L-Phe-derived side chains and bearing appropriate functionalities to be easily applied in peptide chemistry. By means of computational studies, these scaffolds have been demonstrated to act as minimalist peptidomimetics, able to mimic a well defined range of peptide secondary structures and therefore potentially useful for the synthesis of small-molecule PPI modulators. Preliminary biological evaluation of two different resistant hepatocellular carcinoma cellular lines, for which differentiation versus resistance ability seem to be strongly correlated with well defined types of PPIs, has revealed a promising antiproliferative activity for selected compounds.