Kettering University

About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: Cancer & RNA. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.

New Efficient Synthesis of Resorcinylic Macrolides via Ynolides: Establishment of Cycloproparadicicol as Synthetically Feasible Preclinical Anticancer Agent Based on Hsp90 as the Target

Abstract: A program currently ongoing in our laboratory envisions natural macrolide radicicol-based inhibitors targeting the molecular chaperone Hsp90. Such inhibitors can be potential anticancer agents due to their ability to induce the breakdown of a variety of oncogenic proteins. In this account, we first concern ourselves with a vastly important total synthesis of such an inhibitor. We accomplished this via a new approach, which we term the “ynolide method”, directed to the synthesis of resorcinylic macrolides, including cycloproparadicicol and aigialomycin D. The key features of the syntheses involve cobalt-complexation-promoted ring-closing metathesis (RCM) to generate ynolides, followed by Diels−Alder reaction with dimedone-derived bis-siloxy dienes to elaborate the benzo system. A number of interesting analogues were synthesized using this protocol. They were evaluated for their inhibitory activity against the growth of breast cancer cell line, MCF-7. The potency of their cytotoxicity was found to be consis...

Regulation of the Immune Response by T-Cell Subclasses

Abstract: Purified T lymphocytes mediate a wide variety of immunologic functions. These cells can generate cytotoxic responses to alloantigens (Cerottini and Brunner, 1974; Cantor et al., 1975a), exert helper (Transplantation Reviews, 1969) and suppressive (Gershon, 1974) effects on the production of antibody, and initiate graft-vs.-host (Cantor, 1972) and delayed-type inflammatory responses (David and David, 1972). One may ask whether this diversity of function reflects a functional heterogeneity of T cells existing prior to antigen stimulation. According to this model, each T-cell function might be mediated by a subclass of T cells that has been programmed during differentiation to express a single or limited type of immune response. Alternatively, a single mature pluripotent T cell may be induced by antigen to give rise to cells capable of mediating the complete range of T-dependent responses.

A strategy for a convergent synthesis of N-linked glycopeptides on a solid support

Abstract: Oligosaccharides and glycopeptides are of considerable importance in molecular biology and pharmacology. However, their synthesis is complicated by the large number of different linking sites between each saccharide unit, the need for stereochemical control, the chemical sensitivity of the glycopeptide bonds, and the need to harmonize diverse protecting groups. Here, an efficient solid-phase synthesis of three N-linked glycopeptides based on glycal assembly is presented. The peptide domain can be extended while the ensemble remains bound to the polymer. The glycopeptides synthesized here are among the largest N-linked glycopeptides ever accessed by either solution- or solid-phase synthesis.