R2 R1


N N


Zn R2 R2 R1


Scheme 1 The interconversion of conformers of diyne- linked porphyrin dimers [R1


R2 and R2


3-C6H4-(OCH2CH2 OCH3; R1 = 4-C≡C-C5 3-C6H4


= 4-C6H4-N(CH3 +, R2 R2


= 3-C6 H4


CH2 )3 )3


)3 H4 -(OCH2


N-CH3 CH2


)3 OCH3 Coplanar


+, R2 = ]


Scheme 1 R1 R2 cket Scheme 1 Coplanar


Charged section Flat section


Biomedical


KEVIN BURGESS Texas A&M University, US


Small molecule Inhibitors of PD-1•PD-L1 A recent contribution to this section highlighted work by Holak, Domling and others regarding small molecules patented by Bristol Myers Squibb (BMS) for disrupting the PD-1•PD-L1 interaction; the key point of that study was the compounds did not bind the protein-protein interface, but instead at a hydrophobic pocket and this promoted dimerisation of PD-L1.


In their latest contribution,


researchers from these labs describe crystal structures of other BMS leads that bind the same pocket but in different ways (J. Med. Chem., doi: acs.jmedchem.7b00293). The molecules involved (eg 1) are mostly hydrophobic, explaining why they can adopt the cylindrical cavity formed between two PD-L1 molecules.


Cyanine dyes as fluorogenic probes Lemke, Kele, and co-workers have been working on fluorogenic dyes like compound 2 (Bioconjugate Chem., doi: acs.bioconjchem.7b00178). Fluorescence of cyanine


derivatives like this are quenched by the two azide groups, but glow nicely when these groups are clicked with strained alkyne derivatives. Thus, peptides with cyclooctyne groups can be captured via two click reactions to give highly fluorescent


HO3S N SO3H 3 O 1 N3 N+


O 2


site for connection to folate Ar


N+


red-shifted fluorescence to over 800 nm ( )4


( )4


derivatives; this was illustrated using a heptapeptide containing two cyclooctyne residues, and for bridging two GFP units each containing one cyclooctyne introduced via Amber mutations. Fluorescence enhancements in the region of 13x were observed.


fixed varied known preference CONH2 protease


Cyanine dyes with alkyne ‘meso’ substituents Konig and Kramer have prepared cyanine dyes like 3 from the


N H


O O CONH2 protease


N H


O O CONH2 08 | 2017 45 H2N CONH O O SO3H CO2H N N3 OMe


OMe N


H


H N


O


corresponding cyanine dyes with a chloride at the meso position (Chem. Eur. J., doi: chem201700026). This appears to be the first time cyanine dyes with a meso alkyne have been reported and the effects of this substitution are quite interesting: a red shift of the fluorescence emission maxima by about 30nm to over 800nm. Folate was connected to the meso position of these dyes, to target the folate receptor on cancer cells.


Dye toolbox for tracking serine proteases in neutrophils Salvesen, Drag and co-workers have described the development of a set of four probes of intracellular imaging of neutrophils (J. Am. Chem. Soc., 2017, 139, 10115). The conclusion of this paper is


F F HN


interesting: these serine proteases localise in different neutrophil azurophile granules, and the images to show these are spectacular. However, most chemists will be more interested in the approach. Figure 1a shows how a positional


O entrectinib panTrk kinase inhibitor HN O


H N


N N N R2 R1 R1 R2 Twisted R2 R1 R2 R2


substituted arenes, eg R1 R2 R1


are differently -(OCH2


OCH3 =


= H, ;


R2 R1 R2


N N


R1 Zn R2


N N


= R1 R1 R2


Zn R2


R2R2 Twisted R2 R2 R2 R1 R2


N N


= R1


Zn R2


R2 HIGHLIGHTS


screening approach was used to reveal selectivity between the different proteases. Once the selectivity was determined, a task that was not as straightforward as it might have been because there was some overlap, the C-terminal group was exchanged for one that becomes covalently attached. In this way, complementary dyes on a set of peptides that are selective


H2N


CONH


O O CONH


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