Three-stranded mixed artificial beta-sheets.

James S. Nowick, Eric M. Smith, Joseph W. Ziller and A. J. Shaka.

Department of Chemistry, University of California, Irvine, CA 92697-2025, USA


This paper describes the design, synthesis, and structural evaluation of a pair of compounds, comprising molecular templates and attached peptide strands, that mimic a small three-stranded mixed small beta, Greek-sheet (6a and b). Each of these artificial small beta, Greek-sheets is composed of two different molecular templates and two dipeptide strands. One of the templates is based on a 5-amino-2-methoxybenzoic hydrazide group that mimics the hydrogen-bonding functionality of a peptide small beta, Greek-strand and serves as the top strand. This template forms a pattern of hydrogen bonds similar to that of an antiparallel small beta, Greek-sheet with the middle peptide strand. The middle peptide strand forms a pattern of hydrogen bonds similar to that of a parallel small beta, Greek-sheet with the bottom peptide strand. The other template holds the three strands next to each other and is based upon a triurea. In one artificial small beta, Greek-sheet (6a), both the upper and middle urea groups and the middle and lower urea groups are linked by dimethylene (CH2CH2) chains; in the other (6b), the upper and middle urea groups are linked by a dimethylene chain, while the middle and lower urea groups are linked by a trimethylene (CH2CH2CH2) chain. 1H NMR chemical shift and NOE studies establish that both of these compounds fold to adopt a hydrogen-bonded small beta, Greek-sheetlike structure in CDCl3 solution. Chemical shift studies establish that three-stranded mixed artificial small beta, Greek-sheets 6 are more tightly folded than their smaller two-stranded homologues, artificial parallel small beta, Greek-sheet 1 and artificial antiparallel small beta, Greek-sheet 3, as well as their three-stranded homologues with truncated small beta, Greek-strand mimics, artificial small beta, Greek-sheets 5. These studies show that the folding of artificial small beta, Greek-sheets 6 is cooperative, with the interactions between the upper and middle strands and between the middle and lower strands reinforcing each other.