[BIO-09]The synthesis of Ser68 phosphorylated CENP-A

Introduction:
Background & abstract,
Scheme of synthetic route.

Result:
Five peptide preparation,
Native chemical ligation between CENP-A-1 and CENP-A-2,
Native chemical ligation between CENP-A-3, CENP-A-4 and CENP-A-5 on solid-phase,
Native chemical ligation between CENP-A-3, CENP-A-4 and CENP-A-5 in solution-phase,
Native chemical ligation between CENP-A-1-2 and CENP-A-3-4-5,
Desulfurization.

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[BIO-08]Chemoselective peptide stapling via side chain-to-side chain Ser/Thr ligation by development of the crypto-salicylaldehyde ester

Herein, we report the development of side chain-to-side chain Ser/Thr ligation for chemoselective peptide stapling, via utilizing benzofuran moieties as the crypto-salicylaldehyde ester and hydroxyl lysine or Dap-Ser dipeptide as the hydroxyl amino functionality for ligation. We have successfully synthesized three stapled inhibitory peptides with varied length of linkers targeting PSD95 GK domain, showing great enhancement of α-helicity, target-binding affinity and cell-penetrating efficiency.

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[BIO-07]A portable oligonucleotide-based microfluidic device for the detection of VEGF165 in a three-step suspended-droplet mode

We designed a G-quadruplex-based aptasensing platform for the sensitive and selective detection of VEGF165 in aqueous solution and red blood cell solution and could achieve a LOD down to picomolar levels using the conventional fluorometer. The platform could be adapted to our SD-based microfluidic device to allow easy sample introduction, flexible volume range and valve, electrode and light-free manipulation. We anticipate that this portable device could be potentially employed as a monitoring tool of VEGF165 for patients or medical institutes.

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[BIO-05]Cell-permeant fluorescent probes for imaging the activation of a signaling enzyme SARM1

Sterile Alpha and TIR Motif-containing 1 (SARM1) works as a main effector in axon degeneration through its NAD metabolizing activity, which is a potential drug target for many neurological disorders.1-2 Here we designed a series of fluorescent probes for labeling the intercellular enzymatic activity of SARM1. Among them, PC6 and PC11, showed excellent sensitivity and selectivity in vitro. Activity imaging documented for the first time that SARM1 activation precedes fragmentation by several hours. Our study provides a novel method for monitoring the activity of SARM1.

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[BIO-04]Development of advanced photodynamic molecular beacons with multiple controls for targeted photodynamic therapy

Controlling the photoactivity of photosensitizers via tumor-associated stimuli is a promising approach to overcome the non-specific toxicity of photodynamic therapy. The co-called photodynamic molecular beacons (PMBs) are quenched in the native form, but are activated upon interactions with cancer-related stimuli, resulting in restoration in fluorescence emission and reactive oxygen species generation. Two dual activatable zinc(II) phthalocyanine (ZnPc)-based PMBs are reported in this presentation, which are fully activated in the presence of both glutathione and cathepsin B as demonstrated in a buffered solution and a range of cancer cells. The trimeric ZnPc-based PMB has been further conjugated with a tumor-targeting peptide, of which its photobiological properties are also reported.

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[BIO-03]Luminogenic bioorthogonal iridium(III) bis-tetrazine complexes for selective labeling and stapling of BCN-tagged peptides and cell imaging

Three novel luminogenic cyclometalated iridium(III) bis-tetrazine complexes were synthesized and characterized. The applications of these complexes as luminogenic double-clicking two-point binders for the derivatives of a strained alkyne, bicyclo[6.1.0]non-4-yne (BCN) were examined. Selective labeling and stapling of BCN-tagged peptides using the complexes were investigated by HPLC. Live cell imaging using the iridium hydrogel loaded with organic dyes BODIPY-Et and BODIPY-PEG40k was studied.

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[BIO-02]Modulation of emission and singlet oxygen photosensitisation in live cells utilizing bioorthogonal phosphorogenic probes and protein tag technology

The self-labeling protein SNAP-tag is commonly used to study the expression and functions of proteins of interest (POI) in live cells. It undergoes specific reactions with synthetic probes containing a benzylguanine (BG) moiety. Despite the development of many substrates for this protein tag, photofunctional substrates that serve as both fluorogenic probes and singlet oxygen (1O2) photosensitisers have not been reported. Herein, we designed a new class of phosphorogenic iridium(III) nitrone complexes for the two-step labeling of SNAP-tag to confer luminogenic properties and controllable 1O2 generation to the system.

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[BIO-01]Bioorthogonal phosphorogenic rhenium(I) polypyridine sydnone complexes for specific lysosome labeling

The development of new bioorthogonal reactions is necessary for a multitude of biological applications. In this work phosphorogenic rhenium(I) polypyridine sydnone complexes were designed for specific lysosomal labeling. The complexes were non‐emissive, but strain‐promoted sydnone‐alkyne cycloaddition reaction with the substrate BCN‐OH led to emission enhancement in the range of 8.8 to 17.3. Conjugation of the complexes with BCN‐BSA demonstrated emission enhancement factors as high as 38.9. Specific lysosomal labeling in live cells was achieved by using BCN‐morpholine and one of the rhenium(I) complexes.

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