Solid-phase synthesis and dimerization of an azobenzene-containing peptide as photoisomerizable proteinase inhibitor

Rovero, Paolo; Pegoraro, Stefano; Viganò, Stefania; Amato, Cristina; Vaccari, Lucia; Balestreri, Ettore; Felicioli, Romano

doi:10.1007/bf00122920

Cited by 8 publications

(2 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A close value of 64% cis is obtained from the amide signals in the 1 H‐NMR spectra (see Supporting Information). A similar value was previously found for compound 1 (60%) and this value was also reported by others23. The amount of cis present after UV irradiation for compounds 3 and 4 was assumed to be approximately the same as for compound 2 .…”

Section: Resultssupporting

confidence: 88%

Switching between low and high affinity for the Syk tandem SH2 domain by irradiation of azobenzene containing ITAM peptidomimetics

Kuil¹,

Wandelen²,

Mol³

et al. 2009

Journal of Peptide Science

View full text Add to dashboard Cite

Spleen tyrosine kinase (Syk) plays an essential role in IgE receptor signaling (FcepsilonRI), which leads to mast cell degranulation. Divalent binding of the tandem SH2 domain (tSH2) of Syk to the intracellular ITAM motif of FcepsilonRI activates the kinase domain of Syk, and thereby initiates cell degranulation. The inter SH2 domain distance in Syk tSH2 might be important for Syk kinase activation. In this study, photoswitchable ITAM peptidomimetics containing an azobenzene moiety were synthesized. Irradiation of these constructs changes the distance between the two SH2 binding epitopes and therefore, they may be used as photoswitches. The affinity of the cis- and trans-isomer for tSH2 was assayed with SPR. The ITAM peptidomimetic with the smallest linker displayed the largest difference in affinity between the two isomers (at least 100-fold), and the affinity of the cis-isomer was comparable to monovalent binding. The ITAM mimics with larger photoswitchable linkers displayed modest differences. These results indicate that Syk tSH2 is able to adapt the inter SH2 domain distance to ligands larger than native ITAM, but not to smaller ones.

show abstract

Section: Resultssupporting

confidence: 88%

Switching between low and high affinity for the Syk tandem SH2 domain by irradiation of azobenzene containing ITAM peptidomimetics

Kuil¹,

Wandelen²,

Mol³

et al. 2009

Journal of Peptide Science

View full text Add to dashboard Cite

show abstract

“…Most previous research on photoresponsive peptides has used peptides containing the photoresponsive groups in the side chains, although integration, mainly of azobenzene compounds, in the polypeptide backbone, especially of cyclic peptides, has been described (3, 4). The photoisomerization from the trans to the cis form of such peptides has, for example, been used to study the early events in protein folding (5) or the possibility of a modification of enzymatic activity (6–8). A very interesting variant of photomodulating biological activities concerns the possibility of switching the normally very specific antibody−antigen binding.…”

Section: Introductionmentioning

confidence: 99%

Design and Characterization of Stimuli-Responsive FLAG-tag Analogues and the Illumination-Induced Modulation of Their Interaction with Antibody 4E11

et al. 2006

View full text Add to dashboard Cite

An azobenzene group containing beta-amino acid N-Fmoc-4-aminomethyl phenylazobenzoic acid was synthesized and with the exception of the C-terminal amino acid residue was substituted by solid-phase peptide synthesis into all positions of the FLAG sequence (DYKDDDDK), an octapeptide capable of specific interaction with the monoclonal antibody 4E11. The trans state of the beta-amino acid was thermodynamically more stable than the cis state. However, the molecule could be switched into the cis conformation by illumination at 340 nm. Peptides containing the artificial amino acid also became photoresponsive. In the absence of light, the spontaneous back-isomerization into the trans conformation of the photoresponsive was extremely slow (>8 h no significant increase in trans content). When illuminated with visible light (440 nm), the back-isomerization from the cis to the trans state was accelerated and occurred with a half-life of approximately 10 min. The cis form of the photopeptides was more hydrophilic than the trans form, as evidenced by differences in the retention time of the two isomeric forms in reversed-phase chromatography. Photopeptides that contained the intact sequences responsible for binding of the FLAG tag to the antibody, namely, the DYK motive at the N-terminus, showed binding to the antibody in both a dot blot immunoassay and in Biacore binding studies, albeit with lower affinity than the unmodified FLAG sequence. Peptides with a substitution in positions 4-6 showed differences in binding strength between the trans and the cis form in the Biacore studies, no such difference could be observed for the peptide with a substitution in position 7.

show abstract

Biological Formation and Reactions of Hydrazo, Azo and Azoxy Groups

Banthorpe

2009

Patai's Chemistry of Functional Groups

View full text Add to dashboard Cite

show abstract

Solid-phase synthesis and dimerization of an azobenzene-containing peptide as photoisomerizable proteinase inhibitor

Cited by 8 publications

References 14 publications

Switching between low and high affinity for the Syk tandem SH2 domain by irradiation of azobenzene containing ITAM peptidomimetics

Switching between low and high affinity for the Syk tandem SH2 domain by irradiation of azobenzene containing ITAM peptidomimetics

Design and Characterization of Stimuli-Responsive FLAG-tag Analogues and the Illumination-Induced Modulation of Their Interaction with Antibody 4E11

Biological Formation and Reactions of Hydrazo, Azo and Azoxy Groups

Contact Info

Product

Resources

About