Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• ] were one of the earliest examples of folate disulfide–drug conjugates and after the conjugate is internalized by endocytosis, it was demonstrated that the endosomes exert reductive cleavage. For conjugate 7 we found that disulfide cleavage provided a thiol derivative of ansamitocin P-3 (4, AP-3) 8 with

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• , such as in the study of receptor-mediated endocytosis. The protein involved in the endocytosis needs to be translocated from cytoplasm, which has a pH around 7, to the endosomes and lysosomes, which have pH values around 5 [22]. Since the fluorescence of compound 1a is relatively weak at acidic

• conditions, compound 1b and 1c with lower pKa are important and thus synthesized. They will be more fluorescent in an acidic environment, which makes them better probes for endocytosis than compound 1a. With the new synthetic protocol, compound 1b and 1c now can be prepared in a straightforward manner. The

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• toxin conjugates to the plasma membrane, followed by endocytosis and, in most cases, cleavage of the toxin from the carrier. Interestingly, the internalization rate of phalloidin into cells was also significantly increased by the fluorescent moiety tetramethylrhodaminyl, as well as by high molecular

• , into live cells. Keywords: amatoxins; cellular uptake; endocytosis; peptides; phalloidin; phallotoxins; Introduction Phallotoxins and amatoxins, the two families of toxic cyclopeptides produced by the green death cap Amanita phalloides, have been the subject of intense biochemical research for

• pegylated toxin derivatives presented in this study. Internalization and processing The uptake process following the binding step of the phalloidin derivative 3 to the plasma membrane was identified as endocytosis. As shown in Figure 6c, the fluorescent phalloidin is bound on the plasma membrane of mouse