Antifreeze proteins (AFPs) are natural antifreeze molecules that have been found in many organisms including fish, insects, plants, bacteria, and fungi. AFPs exhibit great structural diversity, while they are all characterized by their unique ability to depress the freezing point of water without affecting the melting point apparently. The resulting difference between the melting point and the freezing point, referred to as thermal hysteresis (TH), is generally used as a measure of the antifreeze activities of AFPs. AFPs and co-solutes in body-fluids of cold-adapted organisms are responsible for survival in cold environments. Certain small molecule and macromolecule co-solutes can further enhance the antifreeze activity of AFPs, referred to as enhancers, and they usually do not have TH activity, but can bind to AFP through ionic interactions, hydrogen bonding, and/or hydrophobic interactions. AFP-based antifreeze systems (AFP plus enhancer) are much more effective and their uses are more environmentally friendly in comparison to conventional antifreezes, making them intriguing alternatives to conventional antifreezes in particular in biomedical fields. The proposed research will use series of beetle AFP-small molecule enhancer systems, in which small molecule enhancers display a wide range of antifreeze enhancement abilities. We will determine the binding characteristics between AFPs and enhancers using chemical and biophysical approaches in these systems and unravel the AFP-enhancer affinity in highly efficient AFP systems. We will also determine the factors that can affect the binding in the AFP-enhancers systems. The salt effects will be determined. We will optimize these factors in the proposed functional examinations of the AFP-enhancer systems. Quantitative understanding AFP-based antifreeze systems would help unravel survival strategy in cold-adapted organisms and lead to rational development of highly efficient cold preservation, antifreeze systems for practical biomedical applications, such as in preservation solutions for organ, tissue and cell transplantation, cryopreservation, and cryosurgery.

Public Health Relevance

The proposed work provides a quantitative description of the interactions between enhancer molecules to antifreeze proteins (AFPs) in AFP-based antifreeze systems (AFP plus enhancer). AFP-based antifreeze systems are intriguing alternatives to conventional antifreezes in biomedical fields. This study would help unravel survival strategy in cold-adapted organisms and lead to rational development of highly efficient cold preservation/antifreeze systems in preservation solutions for organ, tissue and cell transplantation, cryopreservation, and cryosurgery.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Continuance Award (SC3)
Project #
2SC3GM086249-08
Application #
9072711
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Alexander, Rashada
Project Start
2009-01-01
Project End
2020-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
8
Fiscal Year
2016
Total Cost
Indirect Cost
Name
California State University Los Angeles
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
066697590
City
Los Angeles
State
CA
Country
United States
Zip Code
90032
Wen, Xin; Wang, Sen; Duman, John G et al. (2016) Antifreeze proteins govern the precipitation of trehalose in a freezing-avoiding insect at low temperature. Proc Natl Acad Sci U S A 113:6683-8
Wang, Sen; Wen, Xin; DeVries, Arthur L et al. (2014) Molecular recognition of methyl ?-D-mannopyranoside by antifreeze (glyco)proteins. J Am Chem Soc 136:8973-81
Wang, Sen; Wen, Xin; Golen, James A et al. (2013) Antifreeze protein-induced selective crystallization of a new thermodynamically and kinetically less preferred molecular crystal. Chemistry 19:16104-12
Wang, Sen; Amornwittawat, Natapol; Wen, Xin (2012) Thermodynamic Analysis of Thermal Hysteresis: Mechanistic Insights into Biological Antifreezes. J Chem Thermodyn 53:125-130
Wang, Sen; Wen, Xin; Nikolovski, Pavle et al. (2012) Expanding the molecular recognition repertoire of antifreeze polypeptides: effects on nucleoside crystal growth. Chem Commun (Camb) 48:11555-7
Wen, Xin; Wang, Sen; Amornwittawat, Natapol et al. (2011) Interaction of reduced nicotinamide adenine dinucleotide with an antifreeze protein from Dendroides canadensis: mechanistic implication of antifreeze activity enhancement. J Mol Recognit 24:1025-32
Amornwittawat, Natapol; Wang, Sen; Banatlao, Joseph et al. (2009) Effects of polyhydroxy compounds on beetle antifreeze protein activity. Biochim Biophys Acta 1794:341-6
Wang, Sen; Amornwittawat, Natapol; Banatlao, Joseph et al. (2009) Hofmeister effects of common monovalent salts on the beetle antifreeze protein activity. J Phys Chem B 113:13891-4
Wang, Sen; Amornwittawat, Natapol; Juwita, Vonny et al. (2009) Arginine, a key residue for the enhancing ability of an antifreeze protein of the beetle Dendroides canadensis. Biochemistry 48:9696-703