Single‐Triggered Trimeric Prodrugs

Abstract

Der Dominoeffekt einer einzigen enzymkatalysierten Reaktion an einer Prodrug‐Plattform leitet den sequenziellen Kollaps des gesamten Systems ein und setzt so die aktiven Wirkstoffeinheiten frei (siehe Schema). Solche dendritischen Systeme könnten zur Verbesserung selektiver chemotherapeutischer Methoden in der Krebstherapie führen.

Self‐Immolative Spacers: Kinetic Aspects, Structure–Property Relationships, and Applications

“…[60] Introducing am ethyl group on the amino group of the spacer (formula 69)a ccelerated cyclization by af actor of 4. Furthermore,a se xpected by the Thorpe-Ingold [42,58] and reactive rotameric effects, [101] mono (formulas 70, 74, 75)and di-(formulas 71 and 72)substitutions in the a position of the ester induced similar accelerations of the cyclization. Such conclusions have been also supported by the "trimethyl lock" effect.…”

“…Enzyme activationp roved to be highly sensitivet o sterich indrance:T he half-life associatedw ithe nzymatic activationb yp lasmind ropped from 42 to 4min whent he activationw as combinedw itht he cyclizationo fN , N ' -ethylenediamine.A ntibody3 8C2-mediateda ctivation by ar etroaldol retro-Michael reactionhas been implementedtoliberate drugs or 4-nitrophenol (entry2,T able 2). [42,45,[100][101][102][103] Penicillin Ga midase (PGA) andB ovine Serum Albumin( BSA) have beenu sedt oc leave the phenylacetamide moiety (entry3,T able2) [34,38,44,45,55,92,96,99,100,[104][105][106][107][108] and ac arbamate [109] (entry 4, Table2), andl iberatev ariouss ubstrates. b-Glucuronidase (b-GUS) [33,40,43] (entry 5, Table2)a nd b-Galactosidase [110][111][112] (entry 6, Table2)h aveb eens uccessfully implementedtospecifically deliver bioactive substrates in tumors and in bacteria.…”

Autoinductive Exponential Signal Amplification: A Diagnostic Probe for Direct Detection of Fluoride

“…Our new DCR probe 1 was constructed of an AB 3 self-immolative dendron [21,22] equipped with silyl ether, the triggering group, which can be cleaved by a fluoride anion (Scheme 1). Removal of this protecting group by fluoride exposes a phenolate, which undergoes rapid disassembly to release a dye reporter and two additional fluorides (Scheme 2).…”

“…Compound 1 b: Compound 1 a [21] (500 mg, 2.25 mmol) was dissolved in DMF (2 mL) and cooled to 0 8C. Imidazole (766 mg, 11.25 mmol) and TBSCl (1.69 gr, 11.25 mmol) were added.…”

Cleavable Dendrimers

“… A heterodendritic dendrimer prodrug that demonstrates tritherapy by the simultaneous delivery of three anticancer drugs by using the catalytic antibody 38C2 as the trigger (based on Ref. 14a). …”