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T»t: COe•.NCILFoiz TosnCC~o Ri:SII:aH( -li-L'..S..1.. I•:C. ~ .7f~~i) Augu st '5, 1951 MEMORANDUM / TO: Drs. Bowden, Feldman, Ford, Hoclf~tt, Jacobson, Somme rs and Stone FROM: h'. U. Gardner RE; .lan F. Chlebowski, Ph.D., Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298 New Application No. 1416 "Calorimetric Investigation of Proteinase-d2Macroglob ulin Interaction." Applicant - Age 38 years; Case Western Reserve Univ. ]969; :.^search Assoc., Univexsity College, London 1969-7]; Research Fellow, Yale, 197i-7h; Research Assoc., Dept. Biochem and A!olecular Biophysics, 1'ale Univ., ]9,76-79; lssist., Prof., Dept. of Biochemistry, Medical College of 1'i rginia, 1979-. Much of' his work has been with NAiR. At Yale he worked with J.E. Coleman. He states his current research interests are "Investigation of the pre-enz)ine forms of proteins of the E. coli periplasmic space;..." ":•lssessment of the thermodynamic stability and mechanism of unfolding of alkaline phos- phatase and other proteins,..." "Determination of tLe role played by the prolirfe residue in controlling structural alteritions of peptides and protei.ns,..." Many of his titles are on metaloenzymes. They are published, for the greater part, in critical journals. Proposal - I had never heard of differential scanning calcsimetry (DSC) before reading this application and anticipated being completely confused. Instead I became somewhat enlightened in a somewhat uncritical way: It is a well organized and nicely written application. He proposes to study the basic structure of alpha-2-macroglobulin (a-2M), a major proteinase inhibitor in the blood. The Geokas group is the only CTR grantee that has been inter- ested in this to any great extent. It is a large molecule; a Zn metalo- enzyme and has been more difficult to study tha!:, the a-l-artti-Pi. He has a very sensitive calorimeter and has done preliminary diffe rential scans that seem informative. Using neuraminidase he will study the effects of remolal or partial removal of oligosaccharides and he will use chelating agents to determine structural changes and functional altera tions following the removal of Zn. The method may permit determination of a-2-M in whole blood plasma. In addition he will use fluorescence probes t o map the proteinase-a-2M interactions. Budget - $17,203 is salary of PI and a technician. $2,250 for perm!-ient equipment. It is a low cost proposal. Comment - I think this should be given careful consideration. It seems to e very basic and to have a very broad application. I rate it high. (I caljed Joseph E. Coleman with whom the applicant worked for several years, Dept. of Molecular Biophysics and Biochemistry, Yale University School of Medicine, 203-436-4942. He was on holiday in August. His s ecretal~y said that she knew that he would support the PI. He might do an ad hoc rc~•iea. Also, 1, noted that J.B. Howard, 1981, PNAS, 79: 2235-38, mi-ht aualif~• in this aea too. I'll chec), up on his location, etc.) lii-