Structure analysis of proteins, peptides and metal complexes by vibrational circular dichroism

Abstract

There are two principal forms of vibrational optical activity (VOA), an IR form referred to as vibrational circular dichroism (VCD) and Raman form known as Raman optical activity (ROA). This paper reports examples of the application of VCD spectroscopy for the determination of the absolute configuration and conformation of chiral molecules, e.g. cyclic -lactams. VCD spectroscopy can be applied for the characterization of the conformation of proteins and peptides in solution. VCD based conformational analysis of cyclic peptides is discussed. Examples are the cyclic hexapeptide cyclo(Pro 2 -Gly-Pro 2 -Gly) and cyclic peptides comprising -homoamino acids (trans-2-aminocyclopentane or trans-2-aminocyclohexane carboxylic acid). Structure analysis by VCD of opiate peptides, glycopeptides, peptidomimetics and chiral transition metal complexes are also discussed.

Anhydrous reverse micelle nanoparticles: new strategy to overcome sedimentation instability of peptide-containing pressurized metered-dose inhalers

“…The obtained CD spectra of aqueous solutions of SCT with SDS, pure sCT, atomized sCT from pMDI formulation and the lyophilized complexes are displayed in Figure 3(E) . It has been well documented that the common regularities of CD spectra of peptides were that α-helix showed a positive characteristic peak near 192 nm and two shoulder peaks at 208 and 222 nm, β-sheet exhibited a negative band near 216 nm and β-corner possessed a positive band at 206 nm (Fort et al, 2002 ; Greenfield, 2006 ; Creasey et al, 2012 ; Hollosi et al, 2012 ).…”

Structure of Condensed Phase Peptides: Insights from Vibrational Circular Dichroism and Raman Optical Activity Techniques

“…Some efforts have been made to model β-turns with designed peptides and to determine if they have characteristic VCD spectra. IR spectra of turns are highly variable, and although some trends have been proposed as diagnostic, unique assignments for turn determination are not reliable. − One approach has been to construct cyclic peptides and try to sort out the overlapping components of the spectra, or prepare sequences that favor turn formation. ,− Paralleling IR, little unique characteristic VCD has developed from these studies, but due to their small size, turn sequences have been subject of detailed theoretical modeling. ,, Turns that are promoted and stabilized by disulfide links have been studied, which can also allow some analyses of the chiral disulfide. ,,, Various other studies of short peptides have been interpreted in terms of turn formation, but the populations of such structures are unclear so that establishing a unique spectral pattern remains difficult. ,,,,,,,, An alternative approach has explored VCD of constrained structures that have cis -amides or are based on cyclic dipeptides, often termed diketopiperazines. ,− Since proteinic peptides are almost universally trans , these studies have been mostly equivalent to small molecule conformational studies, with little impact on more general peptide and protein conformational studies. An unusual aspect of bridged peptides is their potential for constraint-induced nonplanar amide formation, but this also has had little carry-over to “normal” peptides beyond theoretical modeling. ,,, …”

“…In particular, conference proceedings and meeting abstracts are not referenced. How­ever, there are a great many previous reviews in this field, which tend toward a more general nature and provide added back­ground (refs , , , , − , , , − , − , − ). Those that emphasize biopolymer studies with VCD or ROA will be referenced as appro­priate to enable the reader to access older work in more detail, leaving this review to emphasize more focused developments.…”