Gly-Gly-Phe-OH

Protein-mimics are of great interest for their structure, stability, and properties. We are interested in the synthesis of protein-mimics containing triazole linkages as peptide-bond surrogate by topochemical azide-alkyne cycloaddition (TAAC) polymerization of azide- and alkyne-modified peptides. The rationally designed dipeptide N3 -CH2 CO-Phe-NHCH2 CCH (1) crystallized in a parallel β-sheet arrangement and are head-to-tail aligned in a direction perpendicular to the β-sheet-direction. Upon heating, crystals of 1 underwent single-crystal-to-single-crystal polymerization forming a triazole-linked pseudoprotein with Gly-Phe-Gly repeats. During TAAC polymerization, the pseudoprotein evolved as helical chains. These helical chains are laterally assembled by backbone hydrogen bonding in a direction perpendicular to the helical axis to form helical sheets. This interesting helical-sheet orientation in the crystal resembles the cross-α-amyloids, where α-helices are arranged laterally as sheets.

The electronic energy levels of cyclo(glycine-phenylalanine), cyclo(tryptophan-tyrosine) and cyclo(tryptophan-tryptophan) dipeptides are investigated with a joint experimental and theoretical approach. Experimentally, valence photoelectron spectra in the gas phase are measured using VUV radiation. Theoretically, we first obtain low-energy conformers through an automated conformer-rotamer ensemble sampling scheme based on tight-binding simulations. Then, different first principles computational schemes are considered to simulate the spectra: Hartree-Fock (HF), density functional theory (DFT) within the B3LYP approximation, the quasi-particle GW correction, and the quantum-chemistry CCSD method. Theory allows assignment of the main features of the spectra. A discussion on the role of electronic correlation is provided, by comparing computationally cheaper DFT scheme (and GW) results with the accurate CCSD method.