SYNTHESIS AND CONFORMATIONAL ANALYSIS OF HELICAL METALLACYCLICPEPTIDES

Emmy Handy ‘08

Faculty Advisor: Dr. Curran

The helix is an important and commonly occuring secondary structural element in proteins. Because nucleation of a helix in short peptides is entropically unfavorable, it is difficult to study such structures. One method for overcoming this problem is to form a cyclic peptide via a link between side chains of two residues, which induces hydrogen bonding and stablizies helix formation. In this thesis work, stabilization of a peptide helix was achieved using an organometallic compound as the link between side chains. Linear tetrapeptides, Boc-Lys(Cbz)-Ala-Val-Lys(Cbz)-NHMe and Boc-Lys(Cbz)-Met-Ile-Lys(Cbz)-NHMe, were succesfully synthesized via solution phase peptide synthesis, and were cyclized with the organometallic compound, 1,1’-ferrocendediacid chloride. The cyclizing link was achieved by forming amide bonds between the amines on the lysine side chains and the carbonyls of the ferrocene derivative. Analysis of the resulting metallacyclicpeptides by ¹HNMR, COSY, TOCSY, and ROESY experiments indicated that they had adopted the conformation of a 3₁₀ helix. ^SHHNM