89537-10-0Relevant academic research and scientific papers
Antineoplastic activity of linear leucine homodipeptides and their potential mechanisms of action
Lei, Yun,Yang, Xiao-Xia,Guo, Wei,Zhang, Fu-Yong,Liao, Xiao-Jian,Yang, Hui-Fu,Xu, Shi-Hai,Xiong, Sheng
, p. 503 - 512 (2018/06/04)
Galaxamide is a rare cyclic homopentapeptide composed of three leucines and two N-methyl leucines isolated from marine algae Galaxaura filamentosa. The strong antitumor activity of this compound makes it a promising candidate for tumor therapy. The synthesis of galaxamide, however, is a complex process, and it has poor water solubility. On the basis of its special chemical composition, we designed a series of linear leucine homopeptides. Among seven dipeptide derivatives, five compounds with terminal protection groups and methyl substitution of the hydrogen in the amido group showed remarkable inhibitory effects against various cancer cells. N-Tertbutyl-d-leucine-N-methyl-d-leucinebenzyl (A7), the only stereomer condensed by two d-leucines, showed the highest antineoplastic activity. A7-Treated cells showed cell cycle arrest and morphological changes typical of cells undergoing apoptosis. The population of Annexin-V positive/propidium iodide-negative cells also increased, indicating the induction of early apoptosis. A7 promoted the cleavage of caspase-9 and caspase-3, as well as increased intracellular Ca 2+ levels and decreased the mitochondrial membrane potential. Collectively, certain linear leucine dipeptides derived from cyclic pentapeptide are able to inhibit tumor cell proliferation through cell cycle arrest and apoptosis induction. The N-methyl group in the side chain and the d/l conformation of the amino-Acid residue are critical for their activity.
Expanding the limits of isonitrile-mediated amidations: On the remarkable stereosubtleties of macrolactam formation from synthetic seco -cyclosporins
Wu, Xiangyang,Stockdill, Jennifer L.,Park, Peter K.,Danishefsky, Samuel J.
supporting information; experimental part, p. 2378 - 2384 (2012/03/12)
The scope of isonitrile-mediated amide bond-forming reactions is further explored in this second-generation synthetic approach to cyclosporine (cyclosporin A). Both type I and type II amidations are utilized in this effort, allowing access to epimeric cyclosporins A and H from a single precursor by variation of the coupling reagents. This work lends deeper insight into the relative acylating ability of the formimidate carboxylate mixed anhydride (FCMA) intermediate, while shedding light on the far-reaching impact of remote stereochemical changes on the effective preorganization of seco-cyclosporins.
CF3-NO2-PyBOP: A New and Highly Efficient Coupling reagent for N-Methyl Amino Acids
Wijkmans, J.C.H.M.,Blok, F.A.A.,Marel, G.A. van der,Boom, J.H. van,Bloemhoff, W.
, p. 4643 - 4646 (2007/10/02)
1-hydroxy-4-nitro-6-(trifluoromethyl)benzotriazole-containing phosphonium salt CF3-NO2-PyBOP (1h) proved to be a powerful reagent for in situ coupling of N-methylated amino acids.
