Hydrogen bond dipeptide

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-... 

Cheam, T. C., and S. Krimm. 1990. Ab Initio Force Fields of Alanine Dipeptide in Four Non-Hydrogen Bonded Conformations. J. Mol. Struct. (Theochem) 206, 173-203. 

They are of interest in studies on the thermodynamic behavior of nonionic compounds in aqueous media because they have the ability of forming hydrogen bonds with the solvent (through the two r/j-amide groups in the cyclic dipeptide ring), and give rise to hydrophobic interactions. ... 

Enantiomer separation on optically active amino acid, dipeptide, diamide and amide phases by association via hydrogen bonding. " ... 

In summary, the results with pepsin extend the renin data reported by Szelke and Boger and strongly support the postulate of Boger that statine is an analog of a dipeptide tetrahedral intermediate.(20) The C-3 hydroxyl group hydrogen bonds to Asp-213 (220) and Asp-33(35) and displaces a "bound" water molecule from the active site. The isobutyl side chain of statine corresponds to the PI substituent that binds to the SI subsite on the enzyme. The C-1 and C-2 atoms of statine serve to span... 

The role of certain residues in the enzyme mechanism has been confirmed by chemical modification studies, notably for tyrosine. 14 Modification of tyrosyl residues (for example acetylation or nitration) leads to loss of peptidase activity and enhancement of esterase activity. The presence of the inhibitor -phenylpropionate protects two tyrosine residues from acetylation. Those are Tyr-248 and probably Tyr-198, which is also in the general area of the active site. The modified apoenzyme has lower affinity for dipeptides, as might be expected from the loss of hydrogen bonding between Tyr-248 and the peptide NH group. 

The dependence of the principal components of the nuclear magnetic resonance (NMR) chemical shift tensor of non-hydrogen nuclei in model dipeptides is investigated. It is observed that the principal axis system of the chemical shift tensors of the carbonyl carbon and the amide nitrogen are intimately linked to the amide plane. On the other hand, there is no clear relationship between the alpha carbon chemical shift tensor and the molecular framework. However, the projection of this tensor on the C-H vector reveals interesting trends that one may use in peptide secondary structure determination. Effects of hydrogen bonding on the chemical shift tensor will also be discussed. The dependence of the chemical shift on ionic distance has also been studied in Rb halides and mixed halides. Lastly, the presence of motion can have dramatic effects on the observed NMR chemical shift tensor as illustrated by a nitrosyl meso-tetraphenyl porphinato cobalt (III) complex. 

Allott, C., Adams, H., Bernad, P. L., Hunter, C. A., Rotger, C., Thomas, J. A., Hydrogen-bond recognition of cyclic dipeptides in water. Chem. Commun. 1998, 2449-2450. 

---