A topographically and conformationally constrained, spin‐labeled, α‐amino acid: crystallographic characterization in peptides*

Abstract

2,2,6,6-Tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) is a topographically and conformationally restricted, nitroxide containing, C(alpha)-tetrasubstituted alpha-amino acid. Here, we describe the molecular and crystal structures, as determined by X-ray diffraction analyses, of a TOAC terminally protected derivative, the cyclic dipeptide c(TOAC)(2).1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) solvate, and five TOAC-containing, terminally protected, linear peptides ranging in length from tetra- to hepta-peptides. Incipient and fully developed, regular or distorted 3(10)-helical structures are formed by the linear peptides. A detailed discussion on the average geometry and preferred conformation for the TOAC piperidine ring is also reported. The X-ray diffraction structure of an intramolecularly cyclized side product resulting from a C-activated TOAC residue has also been determined.

Crystal Structure of a Spin‐Labeled, Channel‐Forming Alamethicin Analogue

“…[5] Therefore, it is not expected to significantly affect the overall conformation of the alamethicin helical structure. In addition, the TOAC nitroxide moiety, being part of a piperidine ring which includes the C a atom, is tightly connected to the peptide backbone.…”

Conformational properties of angiotensin II and its active and inactive TOAC‐labeled analogs in the presence of micelles. Electron paramagnetic resonance, fluorescence, and circular dichroism studies

“…44,45 Although essentially no change in spectral line shape occurred in the presence of increasing concentrations of zwitterionic HPS for both TOAC 1 -AII and TOAC 3 -AII at pH 4.0 ( Figures 1A and 1B), line broadening was observed in the presence of micelles of negatively charged SDS for both peptides ( Figures 1C and 1D). In addition, while broadening was seen in the spectra of TOAC 1 -AII at the lowest concentrations of the latter detergent, much below its critical micellar concentration (cmc, ca.…”

“…Subsequently, a methodology was developed to insert the paramagnetic residue in midchain positions. 43 The probe's C a -tetrasubstituted cyclic structure favors acquisition of helical structure, as well as turn formation 44,45 and renders the EPR spectra of labeled (macro)molecules highly sensitive to the backbone conformational properties. Owing to these unique characteristics, a large number of studies focusing on peptides, including our own 28,[46][47][48][49][50][51][52][53][54][55][56][57][58] and from a variety of groups [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74] appeared in the literature in recent years.…”

Simulation of electron spin resonance spectroscopy in diverse environments: An integrated approach

“…Spectra were collected ad several temperatures in four different solvents: acetonitrile, chloroform, methanol and toluene. Aib [50][51][52] and TOAC [53,54] are two strongly helicogenic, C α -tetrasubstituted, α-amino acids. The cw-ESR spectra have been compared with their theoretical counterparts pertaining to the deepest energy minima obtained by QM computations (3 10 -and α-helix).…”