Synthesis and Study of Templates for Nucleation of alpha-   Helices
{'Code': '03090003', 'Directorate': {'LongName': 'Direct For Mathematical & Physical Scien'}, 'Division': {'LongName': 'Division Of Chemistry'}}
{'SignBlockName': 'George M. Rubottom'}
This research is being supported by the Organic Synthesis                       Program.  The synthesis of the complex polypeptides and                         proteins that occur in natural systems requires an                              understanding of how nature controls the structure and                          properties of these complex molecules.  This work should help                   to clarify these factors and lead to the design of new                          biologically active compounds to be used in agriculture and                     medicine.                                                                                                                                                       Most theories of protein folding postulate that local regions                   of the protein's amino acid sequence have a higher than average                 tendency to fold or coil to assume sheet or helical structures                  that can then act as nucleation sites for later folding steps                   involving nonlocal interactions.  Hitherto, studies of helix                    formation have been hampered by the failure of most short                       polypeptides to assume detectible sheet or helix structure.  In                 the work, helix nucleation sites in the form of rigid groupings                 of three amides or amide surrogates are to be synthesized and                   bonded to short polypeptide sequences.  With these hybrids, the                 role of chain length, amino acid composition, charge at the                     nucleation site, and solvation will be followed by a variety of                 high field proton nuclear magnetic resonance techniques and by                  circular dichroism.  In addition to the N-terminal helix                        nucleating template that has been developed during the                          preceding project period, C-terminal nucleation templates will                  be synthesized and studied, and the geometry of the N-terminal                  template will be refined.  The aims of these studies include                    estimation of the stabilizing effect of the template on                         adjacent helical polypeptide, determining the geometrical                       features of the growth of short helices, and the degree to                      which the helix-forming tendency of amino acid residues is                      independent of enviroment.  The long range objective of this                    study is the design of protein analogs with predictable folding                 properties, using the concurrently developed thiol capture                      method for protein synthesis to generate `chimeric' small                       proteins that contain covalently incorporated nucleation                        templates.
{'FirstName': 'Daniel', 'LastName': 'Kemp', 'EmailAddress': 'kemp@mit.edu', 'StartDate': '12/01/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Massachusetts Institute of Technology', 'CityName': 'Cambridge', 'ZipCode': '021394301', 'PhoneNumber': '6172531000', 'StreetAddress': '77 MASSACHUSETTS AVE', 'CountryName': 'United States', 'StateName': 'Massachusetts', 'StateCode': 'MA'}
{'Code': '1950', 'Text': 'METHODOLOGY'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8813429.xml'}