Conformational properties of cyclic peptide templates for protein design

Pascal Dumy, Ian Eggleston, Stelian Nicula, Gennaro Esposito, Manfred Mutter

Research output: Chapter in Book/Report/Conference proceedingChapter in a published conference proceeding

Abstract

Selectively addressable topological templates represent a key feature in the de novo design of proteins using the TASP concept (Template Assembled Synthetic Proteins). We recently described synthetic approaches to regioselectively addressable (orthogonally protected) lysine-containing cyclic decapeptides (RAFT molecules) as templates for TASP synthesis. We now report conformational studies of these molecules by combined NMR and molecular dynamics methods. These results demonstrate the presence of beta-turn and beta-sheet like structures which were predicted for conformationally well-defined templates. Such NMR studies are facilitated by access to molecules with several differentially protected lysines which serve to remove the degeneracy of the sequence.

We also compare the results obtained with purely peptidic templates with those from templates incorporating beta-turn mimetics in order to further refine these structural motifs. The usefulness of this approach to design a priori the structure of such restrained cyclic peptides will be discussed along with potential new applications for RAFT molecules in molecular recognition and combinatorial synthesis.
Original languageEnglish
Title of host publicationElectronic Conference on Trends in Organic Chemistry
EditorsHenry Rzepa, Christopher Leach, Joanthan Goodman
PublisherRoyal Society of Chemistry
Publication statusPublished - 31 Dec 1996

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