Peptides structure assignment

The next three sections (Sections 7.7.1, 7.7.2, and 7.7.3) cover fluorescence spectroscopy, I15-18 infrared, and circular dichroism, three powerful approaches to characterize the structure and conformational considerations of synthetic peptides. Section 7.7.1 deals with the use of fluorophores and broad aspects of fluorescence spectroscopy to characterize conformational aspects of peptide structure. In a similar manner, Section 7.7.2 covers a broad aspect of the uses of infrared (IR) techniques to study peptide conformations 19-22 Many IR techniques are discussed, as are approaches for the study of specific peptidic structures including amyloid, p-turn, and membrane peptides. Finally, there is a section on circular dichroism (Section 7.7.3) that covers the major issues of concern for peptide synthetic chemists such as the assignments of a-helix, 310-helix, -sheets and P-turns, and polyproline helices 23-25 There is also a brief description of cyclic peptides. 

Once the NMR spectra of a peptide are assigned the range of techniques mentioned earlier can be used to retrieve information that is valuable in the drug-design process. Clearly the 3D structure of the peptide is of vital importance, and we examine it first. Indeed, as is illustrated in Fig. 4, the assignment and structure determination processes are often completed together. 

We have investigated peptides whose structures were known beforehand from NMR or x-ray spectroscopy and related these structures to 2D-IR spectroscopy. Ultimately, one would like to deduce the structure of an unknown sample from a 2D-IR spectrum. In the case of 2D NMR spectroscopy, two different phenomena are actually needed to determine peptide structures. Essentially, correlation spectroscopy (COSY) is utilized in a first step to assign protons that are adjacent in the chemical structure of the peptide so that J coupling gives rise to cross peaks in these 2D spectra. However, this through-bond effect cannot be directly related to the three-dimensional structure of the sample, since that would require quantum chemistry calculations, which presently cannot be performed with sufficient accuracy. The nuclear Overhauser effect (NOE), which is an incoherent population transfer process and has a simple distance dependence, is used as an additional piece of information in order to measure the distance in... 

As usual, final confirmation of the structure assigned to a peptide lies in its synthesis by a method that must unambiguously give a compound of the assigned structure This problem is discussed in the following section. 

Most work on peptide synthesis, however, has had as its aim the preparation of compounds identical with naturally occurring ones. For this purpose a method must permit the joining together of optically active amino acids to form chains of predetermined length and with a predetermined sequence of residues. Syntheses of this sort not only have confirmed some of the particular structures assigned to natural peptides, but also—and this is more fundamental—have proved that peptides and proteins are indeed polyamides. 

Therefore, we have isolated the two products and have assessed their ability to act as substrates for two y-GH s isolated from chick pancreas and hog kidney. These two hydrolases differentially cleave the poly-y-glutamate chain at two distinct y-glutamyl peptide bonds (Scheme HI, open arrow (hog kidney) and filled arrow (chick pancreas)). The results of these enzyme-catalyzed hydrolyses provides strong evidence for the structures assigned to the reaction products as AMPteGlu-y Glu... 

Tsantrizos YS, Pischos S, Sauriol F. Structure assignment of the peptide antibiotic LP237-F8, a metabolite of Tolypocladium geodes. J Org Chem 61 2118-2121, 1996. 

Theoretical Methods as a Tool for Structure Assignment of Peptides in the Solid State... 

Inv-HETCOR is, in particular, useful in and structure assignment of peptides. At natural abundance of nitrogen-15, the corre-... 

In Chapter 1, we have shown how advanced NMR techniques can be employed for assignment of peptide structure in the soHd state. Number of functions can be deduced when primary composition is known but... 

The synthesis of peptides is of great interest, for, as we shall see, the synthesis of an important natural polypeptide has confirmed the structure assigned to it. 

The above examples of Ala H peptides demonstrate that dynamical spectra are capable of capturing the dynamical behavior of the N-H" - 0=C H-bonds and their vibrational anharmonicities with remarkable accuracy, thus providing definitive assignments of the protonated alanine peptide structures produced in the gas phase. We now turn to the vibrational spectroscopy of even more challenging molecular systems, ionic clusters, displaying large vibrational anharmonicities. Details of our combined IR-PD experimental and theoretical dynamical investigations can be fotmd in [37, 65], where the structures of CP-(Methanol)i 2 and C1 NMA(H20) =o-2 clusters (NMA = A-methy 1-acetamide) have been unraveled... 

Namikoshi, M Sim, F Wook Choi, B., and Rinehart, K.L. (1995) Seven more microcystins from Homer lake cells application of the general method for structure assignment of peptides containing P-dehydroamino add unit(s)./. Org. Chem., 60, 3671-3679. 

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