Linker Hydrophilicity Modulates the Anticancer Activity of RGD–Cryptophycin Conjugates
Most anticancer agents are hydrophobic and can easily penetrate the tumor cell membrane by passive diffusion. This may impede the development of highly effective and tumor-selective treatment options. A hydrophilic β-glucuronidase-cleavable linker was used to connect the highly potent antimitotic agent cryptophycin-55 glycinate with the αvβ3 integrin ligand c(RGDfK). Incorporation of the self-immolative linker containing glucuronic acid results in lower cytotoxicity than that of the free payload, suggesting that hydrophilic sugar linkers can preclude passive cellular uptake. In vitro drug-release studies and cytotoxicity assays demonstrated the potential of this small molecule–drug conjugate, providing guidance for the development of therapeutics containing hydrophobic anticancer drugs.
Synthesis of an Advanced Fragment of (+)-Trienomycinol
The synthesis of the fully functionalized eastern fragment of trienomycins A-F, ansamycin antibiotics is described. A key step involves a peptidic coupling between a sulfonyl aniline and an enantiopure carboxylic acid obtained by a completely diastereosel
Stereochemical assignment of intermediates in the rifamycin biosynthetic pathway by precursor-directed biosynthesis
Natural and semisynthetic rifamycins are clinically important inhibitors of bacterial DNA-dependent RNA polymerase. Although the polyketide-nonribosomal peptide origin of the naphthalene core of rifamycin B is well established, the absolute and relative c
Total syntheses of (+)-trienomycins A and F via a unified strategy
The first total syntheses of (+)-trienomycins A and F, representative members of a new class of cytotoxic ansamycin antibiotics, have been achieved. Key features of the unified synthetic scheme included incorporation of the (E,E,E)-triene unit with concom
Smith III,Barbosa,Wong,Wood
p. 8316 - 8328
(2007/10/03)
Total synthesis of (+)-trienomycins A and F
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Smith III,Smith III, Amos B.,Barbosa,Barbosa, Joseph,Wong,Wong, Weichyun,Wood,Wood, John L.
p. 10777 - 10778
(2007/10/03)
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