Professor
B.S. 1950, Iowa State Univ., M.S. 1951, Ph.D. 1952, Univ. Illinois

Organic Chemistry
Synthetic organic chemistry; new amino-protecting groups; efficient, racemization-free peptide coupling agents; new techniques for rapid synthesis of peptides.

Department of Chemistry, 701 LGRT
University of Massachusetts
710 North Pleasant Street
Amherst, MA 01003-9336

office: 1414 LGRT Tower A
tel: 413-577-2027; fax: 413-545-4490

carpino@chem.umass.edu

Principal Research Interests
 
Basic studies on new α-amino protecting groups, new non-α-(side chain) protectants for amino, hydroxyl and sulfur functionality and new coupling techniques, all with a view to developing new strategies for executing both manual and robotic peptide synthesis is currently what my research group is studying. Although present solid phase techniques are adequate for the synthesis of peptides containing up to about 50 amino acids, the routine synthesis of longer peptides up to the level of small proteins by such methods may require marked changes in current methodology.

Deficiencies in protective-group strategies are recognized for the chain assembly step (α-protection) as well as permanent retention of all non-α-functionalities. The longer the chain and the more random the selection and distribution of the 20-odd common amino acids, the greater are the deficiencies of current non-α-protection strategies. Deblocking of side chains may generate reactive species which can destroy or modify significant portions of long assembled sequences. In addition to studies of protective strategies there is a need for superior coupling techniques applicable to both solution and solid phase syntheses. For longer peptides it is essential to reach or closely approach 100% conversion in the coupling step. Without marked improvements in step-wise solid phase strategies this methodology is not likely to be preferred over the segment coupling of short sequences as the best chemical approach to the assembly of small proteins.

Major attention will continue to be devoted to base- and nucleophile-sensitive α-protectants (Fmoc, Bsmoc- and their second-generation analogs) over their acid-sensitive counterparts (Boc-, Teoc-, etc.). This will allow considerable additional simplification of new instrumentation specifically designed to take advantage of base-labile systems.

“1,1-Dioxonaphtho[1,2-b]thiophene-2-methyloxycarbonyl (α-Nsmoc) and 3,3-Dioxonaphtho[2,1-b]thiophene-2-methyloxycarbonyl (b-Nsmoc) Amino-Protecting Groups,” L.A. Carpino, A.A. Abdel-Moksoud, D. Ionescu, E.M.E. Mansour and M.A. Zewail, J. Org. Chem. 72, 1729-1736 (2007).

“Segment Coupling to Highly Hindered N-Terminal, Alamethicin-Related α-Aminoisobutyric Acid (Aib) Residue,” L.A. Carpino, A.A. Abdel-Maksoud, E.M.E. Mansour and M.A. Zewail, Tetrahedron Letters 49, 7404-7407 (2007).

“Depsipeptide Methodology for Solid-Phase Peptide Synthesis: Circumventing Side Reactions and Development of an Automated Technique via Depsidipeptide Units,” I. Coin, R. Dölling, E. Krause, M. Bienert, M. Beyermann, C.D. Sferdean and L.A. Carpino, J. Org. Chem. 71, 6171-6177 (2006).

“The Uronium-Guanidinium Coupling Reagents. Finally the True Uronium Salts,” L. A. Carpino, H. Imazumi, A. El-Faham, F. J. Ferrer, C. Zhang, Y. Lee, B. M. Foxman, P. Henklein, C. Hanay, C. Mügge, H. Wenschuh, J. Klose, M. Beyermann and M. Bienert. Angew. Chem. Int. Ed., 41, 445-448 (2002).