Saturday, February 16, 2013
Room 306 (Hynes Convention Center)
The adhesive proteins employed by mussels have very specialized amino acid compositions undoubtedly related to the particular challenges of achieving permanent adhesion in the wet marine environment. Mussel adhesive proteins (MAPs) are known to contain high levels of the catecholic amino acid 3,4-dihydroxy-L-alanine (DOPA). Catechols are versatile in a chemical sense, participating in redox reactions, high affinity coordination of metal ions, and strong interfacial activity, leading to important roles for catechols in a variety of biological processes such as pigment formation, neurotransmission, iron sequestration, and in the case of mussel byssal proteins- mechanical adhesion. The rich chemical and biochemical landscape of catechols has led to numerous opportunities for the development biologically inspired materials for a variety of applications. In this talk I will describe our work on mussel-inspired synthetic catechol materials for use in surgical adhesion/wound closure, and in drug delivery. Synthetic catechol polymer medical sealants and adhesives are being developed, exploiting the same cohesive and adhesive interactions of catechols that are believed to be important in mussel adhesion. Examples of surgical applications where these materials are candidates for use in humans, include vascular wound closure and for sealing of spontaneous or fetal surgery-associated cases of fetal membrane rupture. In the area of drug delivery, we are developing a novel catechol polymer conjugates of the proteasome inhibitor bortezomib (BTZ) for pH-sensitive delivery to cancer cells. One design takes advantage of the facile conjugation of BTZ to catechols to form pH-sensitive drug delivery vehicles that are stable and inactive in the bloodstream but dissociate in the acidic tumor interstitium or intracellular environment to liberate the drug, activating its proteasome inhibiting function and thereby potentially increasing the efficacy and reducing the peripheral toxicity of BTZ.