Office: 843-792-9926
Lab: 843-792-9930
Fax: 843-792-4850
Email: bullesee@musc.edu
BSB-740

Research Interests

The research interest of my laboratory is the structure and function relationship of insulin and factors of insulin-like structures. Structurally related proteo-hormones of the insulin family are the metabolic hormone insulin, the hormone of pregnancy relaxin, the testicular Leydig cell derived relaxin-like factor, and invertebrate developmental factors bombyxin (from the brains of the silk worm) and the molluscan insulin-related peptide (from neuroendocrine system of the pond snail). There is no known biological crossreactivity between these insulin-like hormones. The wide variety of biological functions inherent in essentially the same three-dimensional structure implies that the biological function of this family of proteins depends primarily on the side chain distribution.  It is the goal to find the surface features that are crucial for the corresponding hormone and its interaction with its cell membrane receptor. The initial step of this investigation involves the chemical synthesis of these factors and of defined analogs. The syntheses are based upon a novel approach, the site directed disulfide-bond formation, which has been highly successful in the synthesis of insulin, relaxins, relaxin-like factor, and bombyxin. Investigation of the physical chemical and biological properties of the analogs by comparison with natural factors will give insight into their structure-function relationships.  The long-term goal of these studies is that a better understanding of the mode of action of these hormones leads to the subsequent design and synthesis of mimetics. Mimetics of insulins could substitute for the daily injections of insulin-dependent diabetes, and mimetics of bombyxin may become the basis of new pest controls.

Selected Publications

• Büllesbach, E.E. and Schwabe, C. (2001) Synthesis and conformational analysis of the insulin-like 4 gene product. J. Pept. Res., 57(1): 77-83.
• Büllesbach, E.E. and Schwabe, C. (2000) The relaxin receptor-binding site geometry suggests a novel gripping mode of interaction. J. Biol. Chem., 275(45): 35276-35280.
• Fullbright, G. and Büllesbach, E.E. (2000) The receptor binding conformation of bombyxin is induced by alanine (B15). Biochemistry, 39(32): 9718-9724.
• Lundquist, J.T. 4th, Büllesbach, E.E. and Dix, T.A. (2000) Synthesis of neurotensin (9-13) analogues exhibiting enhanced human neurotensin receptor binding affinities. Bioorg. Med. Chem. Lett., 10(5): 453-455.
• Büllesbach, E.E., Rhodes, R., Rembiesa, B. and Schwabe, C. (1999) The relaxin-like factor is a hormone. Endocrine, 10(2): 167-169.
• Büllesbach, E.E. (1999) Bombyxin exhibits an insulin-like response to modification in the N-terminal region of the A chain. J. Pept. Res., 54(1): 12-17.
• Büllesbach, E.E. and Schwabe, C. (1999) Specific, high affinity relaxin-like factor receptors. J. Biol. Chem., 274(32): 22354-22358.
• Büllesbach, E.E., and Schwabe, C. (1999) Tryptophan B27 in the relaxin-like factor (RLF) is crucial for RLF receptor binding. Biochemistry 38 (10): 3073-3078.
• Fullbright, G., Lacy, E.R., and Büllesbach, E.E. (1997) The prothoracicotropic hormone bombyxin has specific receptors on insect ovarian cells. Eur. J. Biochem. 245: 774-780.
• Büllesbach, E.E., Steinetz, B.G., and Schwabe, C. (1996) Chemical synthesis of a Zwitterhormon, insulaxin, and of a relaxin-like bombyxin derivative. Biochemistry 35: 9754-9760.
• Büllesbach, E.E. and Schwabe, C. (1995) A novel Leydig cell cDNA-derived protein is a relaxin-like factor (RLF). J. Biol. Chem. 370: 16011-16015
• Büllesbach, E.E., Yang, S. and Schwabe, C. (1992) The receptor-binding site of human relaxin II: A dual prong-binding mechanism. J. Biol. Chem. 267: 22957-22960.
• Büllesbach, E.E. and Schwabe, C. (1991) Total synthesis of human relaxin and human relaxin derivatives by solid phase peptide synthesis and site directed chain combination. J. Biol. Chem. 266: 10754-10761.