149647-99-4Relevant academic research and scientific papers
Racemization free longer N-terminal peptide hydroxamate synthesis on solid support using ethyl 2-(tert-butoxycarbonyloxyimino)-2-cyanoacetate
Manne, Srinivasa Rao,Thalluri, Kishore,Giri, Rajat Subhra,Paul, Ashim,Mandal, Bhubaneswar
, p. 6108 - 6111 (2015/10/28)
A facile, efficient, racemization-free, and environment friendly protocol for the synthesis of peptide hydroxamic acids directly from carboxylic/amino acids by ethyl 2-(tert-butoxycarbonyloxyimino)-2-cyanoacetate in the presence of DIPEA/DMAP at room temperature is described. The compatibility of this method with Fmoc based solid phase peptide synthesis (SPPS) is also demonstrated by synthesizing three relatively large N-terminal peptide hydroxamic acids on resin. Also, some biologically important hydroxamates are synthesized using this protocol.
Modified cap group suberoylanilide hydroxamic acid histone deacetylase inhibitor derivatives reveal improved selective antileukemic activity
Salmi-Smail, Chanaz,Fabre, Aurélie,Dequiedt, Franck,Restouin, Audrey,Castellano, Rémy,Garbit, Slaveia,Roche, Philippe,Morelli, Xavier,Brunel, Jean Michel,Collette, Yves
experimental part, p. 3038 - 3047 (2010/09/07)
A series of SAHA cap derivatives was designed and prepared in good-to-excellent yields that varied from 49% to 95%. These derivatives were evaluated for their antiproliferative activity in several human cancer cell lines. Antiproliferative activity was observed for concentrations varying from 0.12 to >100 μM, and a molecular modeling approach of selected SAHA derivatives, based on available structural information of human HDAC8 in complex with SAHA, was performed. Strikingly, two compounds displayed up to 10-fold improved antileukemic activity with respect to SAHA; however, these compounds displayed antiproliferative activity similar to SAHA when assayed against solid tumor-derived cell lines. A 10-fold improvement in the leukemic vs peripheral blood mononuclear cell therapeutic ratio, with no evident in vivo toxicity toward blood cells, was also observed. The herein-described compounds and method of synthesis will provide invaluable tools to investigate the molecular mechanism responsible for the reported selectively improved antileukemic activity.
