250684-60-7Relevant academic research and scientific papers
A photocontrolled β-hairpin peptide
Dong, Shou-Liang,Loeweneck, Markus,Schrader, Tobias E.,Schreier, Wolfgang J.,Zinth, Wolfgang,Moroder, Luis,Renner, Christian
, p. 1114 - 1120 (2006)
β-Hairpins constitute the smallest β-type structures in peptides and proteins. The development of highly stable, yet monomeric β-hairpins based on the tryptophan zipper motif was therefore a remarkable success [A. G. Cochran, N. J. Skelton, M. A. Starovasnik, Proc. Natl. Acad. Sci USA 2001, 98, 5578-5583]. We have been able to design, synthesize and characterize a hairpin based on this motif which incorporates an azobenzene-based photoswitch, that allows for time-resolved folding studies of β-structures with unprecedented time resolution. At room temperature the trans-azo isomer exhibits a mostly disordered structure; however, light-induced isomerization to the cis-azo form leads to a predominantly extended and parallel conformation of the two peptide parts, which are linked by the novel photoswitch, [3-(3-aminomethyl)-phenylazo] phenylacetic acid (AMPP). While in the original sequence the dipeptide Asn-Gly forms a type I′ β-turn which connects the two strands of the hairpin, this role is adopted by the AMPP chromophore in our photoresponsive β-hairpin that can apparently act as a β I′-turn mimetic. The β-hairpin structure was determined and confirmed by NMR spectroscopy, but the folding process can be monitored by pronounced changes in the CD, IR and fluorescence spectra. Finally, incorporation of the structurally and functionally important β-hairpin motif into proteins by chemical ligation might allow for the photocontrol of protein structures and/or functions.
Photocontrolled chignolin-derived β-hairpin peptidomimetics
Podewin,Rampp,Turkanovic,Karaghiosoff,Zinth,Hoffmann-R?der
, p. 4001 - 4004 (2015)
The synthesis of novel, chignolin-derived peptides comprising the azobenzene photoswitch [3-(3-aminomethyl)phenylazo]phenylacetic acid (AMPP) is reported. Reversible photoswitching behavior led to folding into β-hairpin-like structures, as unequivocally d
Optimization of Substrate-Analogue Furin Inhibitors
Ivanova, Teodora,Hardes, Kornelia,Kallis, Stephanie,Dahms, Sven O.,Than, Manuel E.,Künzel, Sebastian,B?ttcher-Friebertsh?user, Eva,Lindberg, Iris,Jiao, Guan-Sheng,Bartenschlager, Ralf,Steinmetzer, Torsten
supporting information, p. 1953 - 1968 (2017/11/22)
The proprotein convertase furin is a potential target for drug design, especially for the inhibition of furin-dependent virus replication. All effective synthetic furin inhibitors identified thus far are multibasic compounds; the highest potency was found for our previously developed inhibitor 4-(guanidinomethyl)phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148). An initial study in mice revealed a narrow therapeutic range for this tetrabasic compound, while significantly reduced toxicity was observed for some tribasic analogues. This suggests that the toxicity depends at least to some extent on the overall multibasic character of this inhibitor. Therefore, in a first approach, the C-terminal benzamidine of MI-1148 was replaced by less basic P1 residues. Despite decreased potency, a few compounds still inhibit furin in the low nanomolar range, but display negligible efficacy in cells. In a second approach, the P2 arginine was replaced by lysine; compared to MI-1148, this furin inhibitor has slightly decreased potency, but exhibits similar antiviral activity against West Nile and Dengue virus in cell culture and decreased toxicity in mice. These results provide a promising starting point for the development of efficacious and well-tolerated furin inhibitors.
A photoinducible β-hairpin
Aemissegger, Andreas,Kraeutler, Vincent,Van Gunsteren, Wilfred F.,Hilvert, Donald
, p. 2929 - 2936 (2007/10/03)
A photochromic azobenzene linker was incorporated as a turn element into an amino acid sequence known to fold into a β-hairpin structure in aqueous solution. Oligomer formation when the linker was in its thermodynamically favored trans form prohibited str
α,α-difluorophosphonomethyl azobenzene derivatives as photoregulated phosphoamino acid analogs. 1. Design and synthesis
Park, Seung Bum,Standaert, Robert F.
, p. 6557 - 6560 (2007/10/03)
A series of novel, photoregulated phosphoamino acid analogs based on an azobenzene core bearing an α,α-difluoromethylphosphonate as a hydrolytically stable phosphate isostere have been prepared with N-Fmoc protection for use in peptide synthesis. Classes of reagents analogous to both phosphotyrosine and phosphoserine/threonine were prepared by a common route employing a nitrosoarene/aniline condensation to form the azo linkage and the Cu(I)-promoted coupling of an iodoarene with (diethylphosphono)difluoromethyl cadmium bromide (Burton's method) to introduce the phosphonate moiety.
