269745-72-4Relevant academic research and scientific papers
Iminoboronate-Based Peptide Cyclization That Responds to pH, Oxidation, and Small Molecule Modulators
Bandyopadhyay, Anupam,Gao, Jianmin
, p. 2098 - 2101 (2016)
As a rich source of therapeutic agents, peptide natural products usually adopt a cyclic or multicyclic scaffold that minimizes structural flexibility to favor target binding. Inspired by nature, chemists have been interested in developing synthetic cyclic and multicyclic peptides that serve as biological probes and potential therapeutics. Herein we describe a novel strategy for peptide cyclization in which intramolecular iminoboronate formation allows spontaneous cyclization under physiologic conditions to yield monocyclic and bicyclic peptides. Importantly the iminoboronate-based cyclization can be rapidly reversed in response to multiple stimuli, including pH, oxidation, and small molecules. This highly versatile strategy for peptide cyclization should find applications in many areas of chemical biology.
Dual-fluorescence l -amino acid reports insertion and orientation of melittin peptide in cell membranes
Postupalenko, Viktoriia Y.,Zamotaiev, Oleksandr M.,Shvadchak, Volodymyr V.,Strizhak, Aleksandr V.,Pivovarenko, Vasyl G.,Klymchenko, Andrey S.,Mely, Yves
, p. 1998 - 2007 (2014/01/06)
Monitoring insertion and orientation of peptides in situ on cell membranes remains a challenge. To this end, we synthesized an l-amino acid (AFaa) containing a dual-fluorescence dye of the 3-hydroxyflavone family, as a side chain. In contrast to other labeling approaches using a flexible linker, the AFaa fluorophore, introduced by solid phase synthesis into desired position of a peptide, is attached closely to its backbone with well-defined orientation, and, therefore, could reflect its localization in the membrane. This concept was validated by replacing the leucine-9 (L9) and tryptophan-19 (W19) residues by AFaa in melittin, a well-studied membrane-active peptide. Due to high sensitivity of AFaa dual emission to the environment polarity, we detected a much deeper insertion of L9 peptide position into the bilayer, compared to the W19 position. Moreover, using fluorescence microscopy with a polarized light excitation, we found different orientation of AFaa at L9 and W19 positions of melittin in the bilayers of giant vesicles and cellular membranes. These results suggested that in the natural membranes, similarly to the model lipid bilayers, melittin is preferentially oriented parallel to the membrane surface. The developed amino acid and the proposed methodology will be of interest to study other membrane peptides.
