Dipeptide, conformation

Figure 10.4 Geometrical data for the bioactive conformation of PEPT1 dipeptide substrates proposed by Gebauer et al. The dipeptides conformation is defined by backbone torsion angles t /-i = 142°-165°, C0i = 180°, and (p2 = 262°-303° and the distance between the N-terminus and the C-terminus, c/N c = 5.2-5.6 A [77],...

Figure 9. Histogram showing the distribution function of the scalar product of normalized initial momentum vectors for 21 reactive and 21 nonreactive trajectories for valine dipeptide conformational change.

Villa A, Peter C, van der Vegt NFA (2009) Self-assembling dipeptides conformational sampling in solvent-free coarse-grained simulation. Phys Chem Chem Phys 11 2077-2086... 

Levine The dipeptide conformations we have observed using the lanthanide probes in aqueous solution have all been fairly extended structures with 0, W values of —60° and +140°. We note however that in the case of L-alanyl L-alanyl L-alanine the conformation adopted approaches that of a simple helix (Figure 6). We do not find that the preferred conformation of the L-alanyl L-alanine dipeptide is either the C5 or the C form in aqueous solution. We have not investigated the peptide conformations in non-aqueous solvents using the lanthanides as n.m.r. probes but such systems are reviewed by B. C. Mayo Chem. Soc. Rev. 2 (1) p. 49 (1973). The conformations of the diastereomers of phenylalanyl alanine in chloroform confirm the stereochemistry of the 7-member H-bonded ring (Martinelli, Honiberg, and Sternson Tetrahedron 29, p. 1671, (1973)). 

NEMO has demonstrated its ability to describe accurately both inter- and intramolecular interactions in small systems, including glycine dipeptide conformation profiles, ion-water droplets, and urea transition from nonpla-nar to planar conformation in water. Its applicability to biomacromolecules is not yet known. 

AG Anderson, J Hermans. Microfoldmg Conformational probability map for the alanine dipeptide in water from molecular dynamics simulations. Proteins 3 262-265, 1988. 

Substitution of a dipeptide unit by a cychc dipeptide derivative within a peptide chain can induce certain conformational restraints that may alter the biological response via changing receptor selectivity. A facile procedure for synthesis of pyrazinone ring-containing opioid mimetics [21] has been elaborated, based on the cycHzation of readily available dipep-tidyl chloromethyl ketones [22] (Scheme 6). This method affords 2(IH)-pyrazinone derivatives containing substituents with desired functional groups at positions 3 and 6 in high yield. 

Funasaki, N., Hada, S., and Neya, S., Conformational effects in reversed-phase liquid chromatographic separation of diastereomers of cyclic dipeptides, Anal. Chem., 65, 1861, 1993. 

The three prototype mixed p agonist/S antagonists described in this chapter have excellent potential as analgesics with low propensity to produce tolerance and dependence. The pseudotetrapeptide DIPP-NH2[ ] has already been shown to produce a potent analgesic effect, less tolerance than morphine, and no physical dependence upon chronic administration. In preliminary experiments, the tetrapeptides DIPP-NH2 and DIPP-NH2[T] were shown to cross the BBB to some extent, but further structural modifications need to be performed in order to improve the BBB penetration of these compounds. The Tyr-Tic dipeptide derivatives can also be expected to penetrate into the central nervous system because they are relatively small, lipophilic molecules. In this context, it is of interest to point out that the structurally related dipeptide H-Dmt-D-Ala-NH-(CH2)3-Ph (SC-39566), a plain p-opioid agonist, produced antinociception in the rat by subcutaneous and oral administration [72], As indicated by the results of the NMR and molecular mechanics studies, the conformation of the cyclic p-casomorphin analogue H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] is stabilized by intramolecular hydrogen bonds. There-... 

Fig. 1. Conformational energy diagram for the alanine dipeptide (adapted from Ramachandran et al., 1963). Energy contours are drawn at intervals of 1 kcal mol-1. The potential energy minima for p, ofR, and aL are labeled. The dependence of the sequential d (i, i + 1) distance (in A) on the 0 and 0 dihedral angles (Billeter etal., 1982) is shown as a set of contours labeled according to interproton distance at the right of the figure. The da (i, i + 1) distance depends only on 0 for trans peptide bonds (Wright et al., 1988) and is represented as a series of contours parallel to the 0 axis. Reproduced from Dyson and Wright (1991). Ann. Rev. Biophys. Chem. 20, 519-538, with permission from Annual Reviews.

Cheam, T. C. 1993. Normal Mode Analysis of Alanine Dipeptide in the Crystal Conformation Using a Scaled Ab Initio Force Field. J. Mol. Struct. 295,259-271. 

McAllister, M. A., Perczel, P. Csaszar, W. Viviani, J.-L. Rivail, and I. G. Csizmadia. 1993b. Peptide Models 4. Topological Features of Molecular Mechanics and Ab Initio 2D-Ramachandran Maps. Conformational Data for For-Gly-NH2, For-L-Ala-NH2, Ac-l-Ala-NHMe and For-L-Val-NH2. J. Mol. Struct. (Theochem) 288, 161-179. Mehrotra, P. K., M. Mezei, and D. L. Beveridge. 1984. Monte Carlo Determination of the Internal Energies of Hydration for the Ala Dipeptide in the C7, C5, aR, and Pn Conformations. Int. J. Quantum Chem. Quantum Biol. Symp. 11, 301-308. 

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