1160157-92-5Relevant academic research and scientific papers
Preparation of new alkyne-modified ansamitocins by mutasynthesis
Harmrolfs, Kirsten,Mancuso, Lena,Drung, Binia,Sasse, Florenz,Kirschning, Andreas
, p. 535 - 543 (2014/04/17)
The preparation of alkyne-modified ansamitocins by mutasynthetic supplementation of Actinosynnema pretiosum mutants with alkyne-substituted aminobenzoic acids is described. This modification paved the way to introduce a thiol linker by Huisgen-type cycloaddition which can principally be utilized to create tumor targeting conjugates. In bioactivity tests, only those new ansamitocin derivatives showed strong antiproliferative activity that bear an ester side chain at C-3.
Bioreduction of aryl azides during mutasynthesis of new ansamitocins
Mancuso, Lena,Juerjens, Gerrit,Hermane, Jekaterina,Harmrolfs, Kirsten,Eichner, Simone,Fohrer, Joerg,Collisi, Wera,Sasse, Florenz,Kirschning, Andreas
, p. 4442 - 4445 (2013/09/24)
Supplementing a culture of a mutant strain of Actinosynnema pretiosum that is unable to biosynthesize aminohydroxy benzoic acid (AHBA), with 3-azido-5-hydroxy-benzoic acid and 3-azido-5-amino-benzoic acid, unexpectedly yielded anilino ansamitocins instead
Design, synthesis, and biological activity of isophthalic acid derivatives targeted to the C1 domain of protein kinase C
Af Genn?s, Gustav Boije,Talman, Virpi,Aitio, Olli,Ekokoski, Elina,Finel, Moshe,Tuominen, Raimo K.,Yli-Kauhaluoma, Jari
supporting information; experimental part, p. 3969 - 3981 (2010/01/16)
Protein kinase C (PKC) is a widely studied molecular target for the treatment of cancer and other diseases. We have approached the issue of modifying PKC function by targeting the C1 domain in the regulatory region of the enzyme. Using the X-ray crystal structure of the PKC δ C1b domain, we have discovered conveniently synthesizable derivatives of dialkyl 5-(hydroxymethyl)isophthalate that can act as potential C1 domain ligands. Structure-activity studies confirmed that the important functional groups predicted by modeling were indispensable for binding to the C1 domain and that the modifications of these groups diminished binding. The most promising compounds were able to displace radiolabeled phorbol ester ([3H]PDBu) from PKC α and δ at Ki values in the range of 200-900 nM. Furthermore, the active isophthalate derivatives could modify PKC activation in living cells either by inducing PKC-dependent ERK phosphorylation or by inhibiting phorbol-induced ERK phosphorylation. In conclusion, we report here, for the first time, that derivatives of isophthalic acid represent an attractive novel group of C1 domain ligands that can be used as research tools or further modified for potential drug development.
