Foldamers

Foldamers

Thursday, April 12, 2007

The New York Academy of Sciences

Presented By

 

Organizers: Isaac Carrico, Stony Brook University; Kent Kirshenbaum, New York University

Speakers: William DeGrado, University of Pennsylvania; Daniel H. Appella, NIDDK, NIH; E. James Petersson, Yale University

Recent years have seen an increasing level of dialogue between chemists and biologists, the lines of communication consolidated by the availability of recombinant biotechnology tools for manipulating the chemical structure of genes and the proteins they encode. This has led to an explosion of interdisciplinary activity at the chemistry-biology interface, now coined chemical biology.

The goal of the Chemical Biology Discussion Group is to bring together chemists and biologists working in the New York area who are interested in hearing about the latest ideas in this rapidly growing field. This group will provide a forum for lively discussion and for establishing connections, and perhaps collaborations, between chemists armed with novel technologies and biologists receptive to using these approaches to solve their chosen biological problem.

Abstracts

Toward β-Amino Acid Proteins
E. James Petersson
Yale University

Abstract: Peptides composed of β-amino acids have been shown to adopt stable helices in water and interact with cellular proteins and membranes. However, more sophisticated β-peptide functionality awaits the incorporation of higher order structure. We recently reported the β-dodecapeptide Zwit-1F, which assembles spontaneously in aqueous solution into a highly thermostable octameric complex. We determined the structure of the Zwit-1F octamer by X-ray crystallography and characterized its folding and self-association through circular dichroism, differential scanning calorimetry, analytical ultracentrifugation, and NMR. Zwit-1F functions as a model for the design of second generation peptides with different stoichiometries, more complex topologies, and higher affinities.

Backbone Substitutions to Control the Folding of Peptide Nucleic Acids and Peptoids
Daniel H. Appella
NIDDK, NIH

The ability to manipulate the backbone conformations of oligomeric molecules can be used to promote distinct, folded conformations, and to stabilize relevant conformations for binding to biological targets. In the first part of this presentation, the incorporation of cyclopentane groups and sidechains into the backbone of Peptide Nucleic Acids (PNAs) will be described. These modifications enhance binding of PNA to DNA and RNA target sequences. In the second part of this presentation, the development of a 1,5-substituted triazole unit that promotes a hairpin-like turn conformation in Peptoids will be described.