Conformational Properties of Triazole Foldamers
Title: Conformational Properties of Triazole Foldamers
DNr: SNIC 2016/1-111
Project Type: SNIC Medium Compute
Principal Investigator: Nina Kann <kann@chalmers.se>
Affiliation: Chalmers tekniska högskola
Duration: 2016-03-31 – 2017-04-01
Classification: 10407
Keywords:

Abstract

In the last fifteen years peptidic foldamers have emerged as novel artificial oligomers with properties and structural diversity similar to that of natural peptides. Possessing several interesting and important features which their natural representatives lack, they have a great potential for applications in various fields from nanotechnology to pharmaceutics. Among these, foldamers containing 1,4- and 1,5-substitued triazole amino acids are easily prepared via the Cu- and Ru-catalyzed click reactions and may offer increased side chain variation, but their structural capabilities have not yet been widely explored [1]. This limits their use in efficient rationally designed projects. Earlier we have performed a systematic study exploring the conformational space for the two most important basic units of this set of compounds, the 1,2,4- (4Tzl) and the 1,2,5- (5Tzl) triazole amino acids using quantum chemical exhaustive conformation analysis and solution phase NMR spectroscopy in different solvents [2]. Owing to the computational methods, all possible conformations of these compounds were scanned and their potential minima were located using several theoretical approaches (e.g. B3LYP/6-311++G(2d,2p), wB97X-D/6-311++G(2d,2p) and MP2/6-311++G(2d,2p) ). Results demonstrate that the 5Tzl derivatives have 11 low energy conformers leading to a great structural diversity with relative energies lying close to each other. In contrast, 4Tzl have much lower amount of energetically stable conformers, which in principle offer only extended conformations. Based on these preliminary results, we aim to make progress in two directions, in order to better understand their structural properties: 1. We aim to characterize the conformational properties of all possible chiral building units for both 1,4 and 1,5 triazole amino acids, 2. We aim to build oligomer peptides with folded secondary structures and characterize their properties in view of increasingly complex side chain patterns. To perform this the planned theoritcal calculations would provide the set of secondary structures which these compounds may be capable to form, the relative energy distribution of these structures, and the changes in energetic preference among these as function of the oligomer amino acid sequence. 1. Chiral units For the monomers with chiral side chains we aim to employ high level calculations employing mainly B3LYP/6-311++G(2d,2p), wB97X-D/6-311++G(2d,2p) and MP2/6-311++G(2d,2p) levels of theory. 2. Secondary structures Here we build typical secondary structures, e.g. helices, sheets, turns. These will be prepared using side chains with increasing complexity. The structures will then be submitted to QM calculations using B3LYP, wB97XD functionals and middle sized basis sets, to optimize cpu resources, i.e. 6-31+G(d,p). [1] Johansson, Hermansson, Kann, Nordén, Beke-Somfai: d-Peptides from RuAAC-Derived 1,5-Disubstituted Triazole Units, EJOC 2014, 13, 2703 [2] Kann, Johansson, Beke-Somfai: Conformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids – building units for peptidic foldamers, OBC, 2015, 13, 2776