We describe a novel labeling strategy to site-specifically attach fluorophores, biotin, and proteins to the C terminus of the A1 subunit (CTA1) of cholera toxin (CTx) in an otherwise correctly assembled and active CTx complex. Using a biotinylated N-linked glycosylation reporter peptide attached to CTA1, we provide direct evidence that ~12% of the internalized CTA1 pool reaches the ER. We also ...

Cholera toxin (CT), but not pertussis toxin (PT), treatment of cloned murine CTL inhibited target cell lysis in a dose-dependent fashion. The effects of CT were mimicked by forskolin and cyclic adenosine monophosphate (cAMP) analogues. Inhibition of cytotoxicity by CT and cAMP analogs was mediated in part by attenuation of conjugate formation. Additionally, both CT and cAMP analogs blocked the ...

Hodgkin's disease (HD) is a fatal disorder with the unique histologic features of few dysplastic Hodgkin- and Reed-Sternberg (HRS) cells surrounded by an abundance of nonatypical bystander cells in primary biopsies. By using the first Hodgkin cell line L428 the cytokine receptor CD30 was discovered. CD30 proved to be an excellent target for the diagnoses of CD30+ malignancies and for monoclonal...

Ontak®, a conjugate between IL-2 and a diphtheria toxin fragment, was recently investigated in cancer clinical trials aiming to kill CD25+ regulatory T cells (Tregs). We found that the activity of Ontak® was more complex on Tregs and conventional T cells (Tconvs) than anticipated, including a novel strong influence on dendritic cells (DCs).

The neurotoxic lipopeptide (+)-kalkitoxin was synthesized by a route which employed asymmetric organocopper conjugate addition followed by in situ enolate alkylation to install the anti,anti-1,2,4-trimethyl relationship of the toxin; the synthesis of kalkitoxin required sixteen steps and proceeded in 3% overall yield.

We have shown previously that macromolecules can be nondestructively delivered into cultured cells via folate receptor-mediated endocytosis if the macromolecules are conjugated to folic acid prior to addition to receptor-bearing cells (Leamon, C.P., and Low, P. S. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 5572-5576). Although an intracellular destination of the folate-linked proteins could be ...

Antibody (Ab) responses to polysaccharides (PS), such as Neisseria meningitidis group C PS (MCPS), are characterized as being thymus independent and are restricted with regard to clonotype and isotype expression. PS conjugated to proteins, e.g., MCPS coupled with tetanus toxoid or the diphtheria toxin derivative CRM197, elicit thymus-dependent responses. The present study developed a surface pl...