Proton magnetic resonance and conformational energy calculations of repeat pepetides of tropoelastin: the tetrapeptide

Abstract

Note Added in Proof. After this work was completed and in press, a particularly attractive group theoretical treatment of methyl relaxation has appeared (G. B. Matsen, J . Chem. P h~~s . , in press). This treatment leads to spectral density functions identified with symmetry labels rather than with auto-and cross-correlation. The advantage is to provide a physical interpretation for the pre-and postexponential terms in methyl relaxation behavior characterized by multiple exponentials. Subsequent work from this laboratory will use this development. Reference 6, a generalization of the results in ref 24 and 25, also assumesWe assume here that the only random field mechanism contributing to X is spin-rotation. . Phys., 60, 4590 (1974).The & figures give approximate 95% confidence limits (= two standard deviations), and their size reflects the difficulty to be expected when extracting four such parameters from NMR relaxation data.These effects are analogous to those arising from the term Xin eq 4. If cross correlations were ignored, eq 4 would reducez5 to eq 2. Likewise the presence of dipolar cross correlations in the proton frame provides the possibility for otherwise unobservable effects due to auto and cross correlations in the Droton sDin-rotation mechanism.30 (42) The question oi the effects of cross correlations when the dipolar and spin-rotation are both operative will be discussed in a forthcoming publication. See Abstract:The detailed conformation of a tetrapeptide of tropoelastin, t-Boc-L-Vall-L-Proz-Gly3-Gly4-OMe in CDCI,, has been obtained from a combined analysis of 'H N M R spectra and conformational energy calculations. The observations of Gly, and Gly4 methylene protons as ABX spin systems indicate a fixed conformation similar to a cyclic peptide stabilized by hydrogen bond formation. Temperature dependence and solvent perturbation of N H protons and conformational energy calculations each showed the presence of a @-turn, a ten atom hydrogen-bonded ring involving the Gly4 N H and Val, C=O, and a segment of an antiparallel @-pleated sheet stabilized by a hydrogen bond between the Val, N H and the Gly4 C=O. Conformational angles obtained from the observed )J,CH-NH coupling constants and from conformational energy calculations were in good agreement. The secondary structure of this tetramer is shown to be the same as previously proposed for the high polymer of the tetramer in water at elevated temperature.

Theoretical Conformational Analysis on Elastin Model Tetrapeptide Ac-Val-Pro-Gly-Gly-NHMe

“…That is, the conformations with cis Val-Pro peptide bond are restricted to more specified conformational space than those with trans Val-Pro peptide bond (DC, DA, OF, A*F, A*C, A*A, EC, and EA were allowed for Val-Pro portion with trans peptide bond and 11£ < 3 kcal mol -1 ). These results correspond to the results of conformational analysis for Ac-X-Pro-NHMe 12 · 14 with trans or cis peptide bonds, and show that confor- proposed the type II /J-bend structure at ProGly portion in t-Boc-Val-Pro-Gly-Gly-OMe from temperature dependence of NH chemical shift (d<5/dT) in CDCl 3 (with 20% C 6 D 6 ), 6 and HCO-Val-Pro-Gly-Gly-OMe by the NOE measurements in DMSO-d 6 • 7 As mentioned in Results section, the calculated bend probabilities for Ac-Val-Pro-Gly-Gly-NHMe at Pro-Gly portion are 0.171 for type II and 0.429 for type V which is a distorted type II bend, respectively. Total bend probability of type II and type V exceed 0.60.…”

Quantum Molecular Modeling of the Elastinic Tetrapeptide Val-Pro-Gly-Gly

“…they apperar 54 times in bovine elastin (2). Among these the very simple peptide Val-Pro-Gly-Gly has been widely studied as protected monomer (Boc-Val-Pro-Gly-OMe) and polymer by Urry and coworkers (13,14), who evidenced as main structural feature the presence of a type II ~-turn.…”

A stereochemically‐constrained enkephalin analog

“…Earlier studies have shown that the C"H2 protons of both Gly* and Gly3 in Mets-enkephalin are nonequivalent m Hz0 and (CD,),SO, suggesting that the molecules are inflexible on a chemical shift time scale. Non-equivalence of the C&H2 protons of Gly residues has also been used to support the view that ordered conformations exist in solution, for a tetrapeptide fragment of tropoelastin Boc-Val-ProGly-Gly-OMe [27]. While geminal non-equivalance of the C&H2 protons of Gly3 and the CH3 groups of Aib*, is not conclusive evidence for the presence of I-'lg.2.…”