Rational design of potent recrystallization inhibitors

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Antifreeze glycoproteins (AFGPs) are a sub-class of naturally occurring biological antifreezes. AFGP 1 is the largest fraction (33.7 KDa) and AFGP 8 (2.6 KDa, figure 1) is the lowest molecular weight fraction. These compounds are found predominately in Teleost fish and protect these organisms against cryoinjury and death by preventing the uncontrolled growth of seeded ice crystals in vivo.      During the past several years our laboratory has been actively involved in the rational design and synthesis of carbon-linked (C-linked) AFGP analogues possessing enhanced chemical and biological stability as well as increased antifreeze activity.  This class of compounds is ideally suited for cryopreservation applications as they do not exhibit any cytotoxicity and inhibit caspase enzymes in vitro.  The studies described in this proposal will employ well-developed synthetic methodologies to synthesize a series of C-linked AFGP analogues which when tested for activity, will identify the key structural attributes necessary to inhibit the recrystallization of ice in tissues.  With this information we will be able to design the "ultimate" C-linked AFGP analogue suitable for medical, commercial and industrial applications.     Graduate and undergraduate students training in this interdisciplinary environment will acquire essential skills in scientific experimentation, organic synthesis and cell biology preparing them for successful careers in the biopharmaceutical and chemical manufacturing industries as well as academic research.