167423-53-2Relevant academic research and scientific papers
Synthesis and binding properties of a macrobicyclic receptor for N-protected peptides with a carboxylic acid terminus
Henley, Peter D.,Waymark, Christopher P.,Gillies, Iain,Kilburn, Jeremy D.
, p. 1021 - 1031 (2007/10/03)
A novel macrobicyclic receptor, 3, has been synthesised by linking together a diaminopyridine with suitable amino acids, followed by a double intramolecular cyclisation of a suitably activated precursor. Macrobicycle 3 features a diamidopyridirie unit, designed to serve as a specific binding site for carboxylic acid functionality, at the base of an open, bowl-shaped cavity. Incorporation of additional amide functionality around the rim of the bowl-shaped structure provides further hydrogen bonding sites to interact with pcptidic guests. The binding properties of 3 with N-protected amino acid and peptide derivatives have been investigated by NMR titration experiments, which reveal that 3 is a strong and selective receptor for peptides with a carboxylic acid terminus in CDCl3 solution, the strongest binding being observed with Cbz-β-alanyl-D-alanine (-ΔGass = 22.8 kJ mol-1). The macrobicycle is reasonably enantioselective (Cbz-β-alanyl-L-alanine, -ΔGass = 19.1 kJ mol-1) and notably the binding of Cbz-β-alanyl lactic acids is considerably weaker than the binding of the corresponding Cbz-β-alanyl alanines (ΔΔGass ～ 8-9 kJ mol-1). Molecular modelling and 2D NMR studies have been carried out on the free macrobicycle and the 1:1 complex formed with the most strongly bound substrate (Cbz-β-alanyl-D-alanine). These studies provide a consistent picture of the macrobicycle as a flexible receptor, which is able to bind the Cbz-β-alanyl-D-alanine substrate in the macrobicyclic cavity with a series of well defined hydrogen bonds to the alanylalanine amide, and less well defined hydrogen bonds to the benzylcarbamate functionality. The Royal Society of Chemistry 2000.
Synthesis and peptide binding properties of a C2 symmetric macrobicycle
Waymark, Christopher P.
, p. 3051 - 3054 (2007/10/02)
A novel macrobicycle featuring an amidopyridine unit as a carboxylic acid binding site, and amide functionality to provide further hydrogen bonding interactions with suitable guests has been prepared. The ability of this novel macrobicycle to bind peptide derivatives has been investigated.
