Solution Conformation Of Peptide Research Articles

Conformations of peptides in solution by nuclear magnetic resonance spectroscopy. Part 5. Homoallylic proton spin coupling in linear peptides

Five bond proton spin coupling, 5J(HH), has been observed in some linear di- and tri-peptides with trans peptide bonds. Magnitudes of 5J(HH) were analysed in terms of homoallylic coupling using N-methylacetamide and NN-dimethylacetamide as standard compounds for groups antiperiplanar across peptide bonds. Together with 3J(HNCH) magnitudes the results for 5J(HH) can be used to limit the range of conformations (ϕ,ψ) for peptides in solution. Attention has been focused on two peptide conformations studied by 100 MHz 1H n.m.r. measurements of N-acetyl-L-alanyl-N-methylamide (C7 structure) and N-acetyl-L-valyl-glycyl-N-methylamide (β-turn) in different solvents. The conformational properties are compared with previous studies using X-ray crystallography, theoretical calculations, and spectroscopy (n.m.r., i.r.).

Conformations of peptides in solution by nuclear magnetic resonance spectroscopy. Part III. Cyclic dipeptide ring conformations

The determination of the degree of folding (β) of the diketopiperazine ring (DKP) of cyclic dipeptides from 3J(HNCH) and 5J(HH), the homoallylic coupling across peptide bonds, is discussed. From measurements of the 100 MHz 1H n.m.r. spectra of cyclic dipeptides containing glycine or sarcosine[i.e. cyclo-Gly(Sar)-X where X = amino acid] it is concluded that β increases with the bulkiness of amino-acid X for both D2O and DMSO solutions. The results are in agreement with those determined from the c.d. spectra of the same cyclic dipeptides in aqueous solution. A correlation is observed between the magnetic non-equivalence of the Gly (or Sar) methylene group and the degree fo folding of cyclic dipeptides containing amino-acids not substituted by aromatic rings at the β-carbon atom.

Conformations of peptides in solution by nuclear magnetic resonance spectroscopy. Part IV. Conformations of valinomycin determined from homoallylic proton coupling across peptide bonds

100 MHz Proton magnetic resonance measurements have been made on valinomycin in the complexed and uncomplexed form in polar [CD3OD, (CD3)2N·CDO] and non-polar (CDCl3) solutions. A small five-bond long-range coupling was observed between α-CH groups across the peptide bonds of the L-Lac-L-Val and D-Hylv-D-Val molecular fragments. Observation of 5J(HH) enables the L- and D-Val α-CH proton signals to be assigned conveniently. Analysis of 5J(HH) in terms of homoallylic coupling provides information on peptide conformational angles ϕ and ψ, i.e. for valinomycin ψ(L-Lac), ϕ(L-Val), ψ(D-Hylv), ϕ(D-Val). The results for both complexed and uncomplexed valinomycin are compared with those of recent crystal structure analyses and with conformational models of these systems in polar and non-polar solvents.

Conformations of peptides in solution by nuclear magnetic resonance spectroscopy. Part II. Homoallylic coupling in cyclic dipeptides

Using the crystal structure data of numerous cyclic dipeptides the scope of analysing 5,J(HH) of peptides in terms of homoallylic coupling is discussed. From the observed correlation between 3J(HNCH) and 5J(HCαNC′CαH) of cyclic dipeptides in DMSO and CDCl3 solutions it is shown that five bond coupling can be rationalised in terms of homoallylic coupling. Assuming the same angular dependence for 5J(HH) for peptides in all solvents, the conformational properties of the substituted diketopiperazine rings are determined for cyclic dipeptides in different solvents; in particular, detailed conformational properties are discussed for cyclic dipeptides in D2O solutions where 3J(HNCH) cannot be observed. The analysis is extended to explain changes with conformation in observed 5J(α-CH,NR) of N-substituted cyclic dipeptides (R = CH3 or δ-CH2 of proline).

Immunochemistry of sperm whale myoglobin—XIV. Role of histidines 12 and 24 in the antigenic structure

A peptide comprising the sequence 1–31 in sperm-whale myoglobin (Mb) was isolated as one of the peptides from the specific cleavage of Mb at arginine peptide bonds. This peptide had previously been shown (Singhal and Atassi, 1971) to contain the single antigenic reactive region in the entire sequence 1–55. This was previously narrowed down to fall within (but not including all of) sequence 8–30. Carboxymethylation of peptide 1–31 with iodoacetic acid yielded a homogeneous derivative (CM 1–31) which has modified specifically at histidines 12 and 24. One histidine was carboxymethylated at position 3 in the imidazole ring and the other histidine was carboxymethylated at both position 1 and 3. Peptide 1–31 and CM 1–31 had identical ORD and CD parameters, clearly indicating that the modification did not result in a change of the peptide conformation in solution. This ruled out any conformational effects on the immunochemical behavior of the derivative. The antigenic reactivities of peptide 1–31 and CM 1–31 were quantitatively identical when determined with three different antisera to Mb. From previously reported work and the present results, the antigenic reactive region in the first third of the Mb molecule (sequence 1–55) has been shown to be located within (but may not include all of) sequence 13–23. Also, most likely glycine 23 will not participate in interaction with antibody.

Conformations of peptides in solution by nuclear magnetic resonance spectroscopy. Part I. Application of nuclear magnetic double resonance spectroscopy to the determination of cis- and trans-conformations of peptide bonds

The 100 MHz 1H n.m.r. spectra of some N-substituted amides and linear peptides have been measured. A small five-bond, long-range spin coupling has been shown to exist between groups antiperiplanar to each other across the amide and peptide bonds. In certain cases, 5J(HH) has been observed between groups with a syncoplanar arrangement such that 5J(HH)anti > 5J(HH)syn. The observation of 5J(HH) was used to assign the cis- and/or trans-conformations of peptide bonds in linear peptides containing N-methylated amino-acids. For unsubstituted peptide bonds the observation of 5J(HH) between the Cα protons of adjacent amino-acids provides a direct method to confirm the presence of the trans-isomer of the peptide bond in linear or cyclic peptides in aqueous solutions.

The combination of nuclear-magnetic-resonance spectroscopy and potential-energy calculations in the study of peptide conformation in solution.

The combination of nuclear-magnetic-resonance spectroscopy and potential-energy calculations in the study of peptide conformation in solution.