Conjugation of anti-HIV gp41 monoclonal antibody to a drug capable of targeting resting lymphocytes produces an effective cytotoxic anti-HIV immunoconjugate.

HIV-infected cells persisting in the face of suppressive antiretroviral therapy are the barrier to curing infection. Cytotoxic immunoconjugates targeted to HIV antigens on the cell surface may clear these cells. We showed efficacy in mouse and macaque models using immunotoxins, but immunogenicity blunted the effect.

Novel DNA-based T-Cell Activator Promotes Rapid T-Cell Activation and Expansion.

Autologous chimeric antigen receptor engineered T-cell therapies are beginning to dramatically change the outlook for patients with several hematological malignancies. Yet methods to activate and expand these cells are limited, often pose challenges to automation, and have biological limitations impacting the output of the injectable dose. This study describes the development of a novel, highly flexible, soluble DNA-based T-cell activation and expansion platform which alleviates the limitations of current technologies and provides rapid T-cell activation and expansion.

Disubstituted pyrimidines as Lck inhibitors.

We have developed a family of 4-benzimidazolyl-N-piperazinethyl-pyrimidin-2-amines that are subnanomolar inhibitors of Lck. A subset of these Lck inhibitors, with heterocyclic substituents at the benzimidazole C5, are also low-nanomolar inhibitors of cellular IL2 release.

Direct site-specific radiolabeling of an Affibody protein with 4-[18F]fluorobenzaldehyde via oxime chemistry.

Purpose: In this study, we introduce a methodology for preparing 18F-labeled Affibody protein, specifically 18F-Anti-HER2 dimeric Affibody (14 kDa), for in vivo imaging of HER2neu with positron emission tomography (PET).

Procedures: We have used 4-[18F]fluorobenzaldehyde as a synthon to prepare 18F-Anti-HER2 Affibody. Aminooxy-functionalized Affibody (Anti-HER2-ONH2) was incubated with 4-[18F]fluorobenzaldehyde in ammonium acetate buffer at pH 4 in the presence of methanol at 70 degrees C for 15 min.

Dual-surface-modified bacteriophage MS2 as an ideal scaffold for a viral capsid-based drug delivery system.

With the development of covalent modification strategies for viral capsids comes the ability to convert them into modular carrier systems for drug molecules and imaging agents. With this overall goal in mind, we have used two orthogonal modification strategies to decorate the exterior surface of genome-free MS2 capsids with PEG chains, while installing 50-70 copies of a fluorescent dye inside as a drug cargo mimic. Despite the very high levels of modification, the capsids remained in the assembled state, as determined by TEM, size-exclusion chromatography, and dynamic light scattering analysis.

Dual-surface modification of the tobacco mosaic virus.

The protein shell of the tobacco mosaic virus (TMV) provides a robust and practical tubelike scaffold for the preparation of nanoscale materials. To expand the range of applications for which the capsid can be used, two synthetic strategies have been developed for the attachment of new functionality to either the exterior or the interior surface of the virus. The first of these is accomplished using a highly efficient diazonium coupling/oxime formation sequence, which installs >2000 copies of a material component on the capsid exterior.

Interior surface modification of bacteriophage MS2.

An efficient strategy for the interior surface functionalization of MS2 viral capsids is reported, featuring a new hetero-Diels-Alder bioconjugation reaction. After virus isolation, the RNA genome was removed from the spherical particles by exposure to pH 11.8 conditions for a period of 4 h.