Novel Biomaterials with Potential Antibacterial and Adhesive/structural Properties from Ascidians (=Tunicates)

PI: Manackam Sugumaran, Univ. of Massachusetts - Boston, William Robinson, Univ. of Massachusetts - Boston

Project Number:2002-RB-56

Start Date:2002-03-01End Date:2004-02-28

Proposal Summary

Objectives: We propose to a) examine the mechanism of polymerization and its derivatives, and b) develop tunichromes as biopolymerizing for the synthesis of biomaterials with unique antibacterial as well as adhesive/structural properties that will be useful for the biomedical industry.

Methodology: Tunichrome will be isolated, and tunichrome derivatives and model tripeptides (e.g. gly-dopa-dopa, gly-dopa-methylester) will be prepared using published procedures, we have routinely used in our laboratories. All of these compounds will be tested for antibiotic properties by standard antimicrobial assays, and two potential mechanisms of toxic action will be investigated: 1) as cross linkers they could bind to cellular macromolecules, or 2) they could cause oxidative stress due to the presence of the potentially reactive catecholic groups. All dehydro derivatives will be subjected to oxidative polymerization studies with and without a) test proteins such as ribonuclease, albumin, etc., b) cellulose, mucopolysaccharides, etc., and c) DNA. The progress of polymerization will be monitored by SDS-PAGE, agarose electrophoresis, HPLC and other related techniques. The possible incorporation of vanadium ions into the tunichrome-polymerized biopolymers will be investigated using ICP-MS. Oxidative stress caused by these compounds will be evaluated by measuring the reactive oxygen species such as superoxide anions and hydroxyl radicals using biochemical assays designed to trap and/or detect these free radicals.

Rationale: Tunichromes and their derivatives could form potentially useful biomaterials that possess both antibacterial and adhesive/polymerization properties since these two apparently diverse characteristics are actually closely linked biochemically. These related characteristics would make tunichrome a highly useful compounds for the biomedical industry. We envision the in situ synthesis of biomembranes with inherent antimicrobial properties that would find applications in accident triage, emergency medical treatment and surgery, as well as for minor wound repair. Non medical uses could entail the production of antifouling panels for marine and freshwater construction. Moreover, the detailed mechanisms that we will learn from our studies will be directly applicable for the "Green" formulation of environmentally safe products with inherent antipredator, antibacterial and antifouling properties.

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