Chemically Synthesized Molecules with the Targeting and Effector Functions of Antibodies

Abstract

This article reports the design, synthesis, and evaluation of a novel class of molecules of intermediate size (approximately 7000 Da), which possess both the targeting and effector functions of antibodies. These compounds—called synthetic antibody mimics targeting prostate cancer (SyAM-Ps)—bind simultaneously to prostate-specific membrane antigen and Fc gamma receptor I, thus eliciting highly selective cancer cell phagocytosis. SyAMs have the potential to combine the advantages of both small-molecule and biologic therapies, and may address many drawbacks associated with available treatments for cancer and other diseases.

Chemical Tools To Monitor and Manipulate Adaptive Immune Responses

“…David Spiegel and colleagues have applied the chemical dimerizer concept to the goal of recruiting immune effector function to target cells that they wish to eliminate 17,38,39 , marking the first experimental realization of the concept shown in Fig. 7A.…”

“…If there is a sufficiently high concentration of the target receptor on the cell surface, the antibody can recruit effector functions, such as the complement cascade or cytotoxic T cells, to kill the target cell. These workers have demonstrated the efficacy of this approach in vitro 38 and in a mouse xenograft model for prostate cancer 39 . So in order to edit epitope-specific immune responses in general, and develop highly selective drugs for CLL in particular, one possibility is to create DNP- or rhamnose-epitope surrogate conjugates.…”

iBodies: Modular Synthetic Antibody Mimetics Based on Hydrophilic Polymers Decorated with Functional Moieties

“…[3] Recently,c hemically synthesized small molecules that fulfill some functions of antibodies have been described. [4] Polymers capable of molecular recognition of other molecules were described several decades ago.T hese molecularly imprinted polymers (MIPs) are based on structure complementarity with the target molecules and are used as molecular biosensors and binders. [5] We set out to develop novel antibody mimetics based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates decorated with three different low-molecularweight ligands.W ec hose water-soluble and biocompatible HPMA copolymers since they have been used for the development of drug delivery vectors,i maging agents,a nd polymer drugs.…”

How to minimalize antibodies

“…Small molecules that mimic the pharmacological properties of mAbs therefore have the potential to become highly competitive drugs. Writing in the Journal of the American Chemical Society, McEnaney et al 2 provide evidence that this is an achievable goal.…”

“…It 2 now report a quadripartite synthetic antibody that is 20 times smaller than naturally occurring antibody molecules and readily generated by chemical synthesis. Cartoon versions of the antibody and the small molecules are approximations of the actual molecular structures and not drawn to scale.…”