Synthesis of Homopolymers and Copolymers Containing an Active Ester of Acrylic Acid by RAFT: Scaffolds for Controlling Polyvalent Ligand Display.

We describe the synthesis of activated homopolymers and copolymers of controlled molecular weight based on the controlled radical polymerization of N-acryloyloxysuccinimide (NAS) by reversible addition fragmentation chain transfer (RAFT). We synthesized activated homopolymers in a range of molecular weights with polydispersities between 1 and 1.2.

Thiol-mediated anchoring of ligands to self-assembled monolayers for studies of biospecific interactions.

We report a method to immobilize thiol-containing ligands onto self-assembled monolayers (SAMs) of alkanethiolates presenting chloracetylated hexa(ethylene glycol) groups. The chloroacetyl groups react with thiols under mild basic conditions, enabling the stable immobilization of biologically active ligands in a well-defined orientation. These SAMs on gold are well suited for studies of biospecific interactions of immobilized ligands with proteins and cells.

Synthesis of polyvalent inhibitors of controlled molecular weight: structure-activity relationship for inhibitors of anthrax toxin.

We describe a novel method to synthesize activated polymers of controlled molecular weight and apply this method to investigate the relationship between the structure and activity of polyvalent inhibitors of anthrax toxin. In particular, we observe an initial sharp increase in potency with increasing ligand density, followed by a plateau where potency is independent of ligand density. Our simple strategy for designing polyvalent inhibitors of controlled molecular weight and ligand density will be broadly applicable for designing inhibitors for a variety of pathogens and toxins, and for elucidating structure-activity relationships in these systems.

Synthesis of copolymers containing an active ester of methacrylic acid by RAFT: controlled molecular weight scaffolds for biofunctionalization.

We report the controlled radical copolymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) with a monomer containing an active ester, N-methacryloyloxysuccinimide (NMS), by reversible addition fragmentation chain transfer (RAFT). The large difference in the reactivity ratios of HPMA and NMS resulted in significant variations in copolymer composition with increasing conversion during batch copolymerization. The use of a semi-batch copolymerization method, involving the gradual addition of the more reactive NMS, allowed uniformity of copolymer composition to be maintained during the polymerization.

Design of water-soluble, thiol-reactive polymers of controlled molecular weight: a novel multivalent scaffold.

Multivalent molecules, i.e. scaffolds presenting multiple copies of a suitable ligand, constitute an emerging class of nanoscale therapeutics.