Synthesis and Characterization of DOPA-PEG Conjugates

Introduction Mussel adhesive proteins (MAPs) are remarkable underwater adhesive materials which form tenacious bonds between certain marine organisms and the substrates upon which they reside. These proteins are secreted by the organisms as fluids which undergo a crosslinking or hardening reaction which leads to the formation of a solid adhesive plaque. One of the unique features of MAPs is the presence of L-3,4-dihydroxyphenylalanine (DOPA), an amino acid which is believed to be responsible for both adhesion and crosslinking characteristics of MAPs. Oxidation of DOPA to the o-quinone can lead to crosslinking (e.g. by Michael addition with a primary amine), whereas the catechol form of DOPA is believed responsible for adhesion to substrates. However, complexation between DOPA and metal ions could also contribute to bulk crosslinking as well as adhesion. For example, Fe forms extremely stable coordination complexes with a variety of catechols, and bisand triscatecholate complexes have been observed to form between Fe and a MAP from Mytilus edulis. Recently, DOPA-containing synthetic polypeptides have been synthesized by copolymerization of N-carboxyanhydride monomers of lysine and DOPA. The water soluble copolymers were found to form gels in the presence of oxidizing agents, and adhesion to metal substrates was observed. Our interest is in developing DOPA-containing synthetic polymers for use as biomaterials. We hypothesize that the adhesive, metal ion binding, and crosslinking characteristics of DOPA can be exploited for development of new hydrogels as tissue adhesives and drug delivery matrices. In this paper we describe our preliminary efforts toward the synthesis and characterization of linear and branched DOPA-poly(ethylene glycol) conjugates (DOPA-PEGs).