Indole moiety induced biological potency in pseudo- peptides derived from 2-amino-2-(1H-indole-2-yl) based acetamides: synthesis, structure and computational investigations (original) (raw)
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Structure and optical activity of unsaturated peptides
Journal of the American Chemical Society, 1975
a,@-Unsaturated amino acid residues are present in many microbial peptides having antibiotic activity; however, their stereochemistry has not been investigated in detail. In this work 18 N-acylated a,@-unsaturated peptides (dehydropeptides) containing one or two dehydrophenylalanine (dehydro-Phe) residues and a C-terminal optically active L-amino acid or amine residue have been prepared. The structure CH3CO[NHC(CHC6H5)CO].N"RIR2 ( n = 1 and 2) with trans configuration of the double bond in the dehydro-Phe moiety has been demonstrated by NMR, ir, and uv absorption and X-ray diffraction. Monounsaturated peptides show low-intensity CD bands strongly affected by the nature of R , and R2. On the contrary, doubly unsaturated derivatives show CD curves with strong Cotton effects and evidence of exciton splitting with a negative couplet in the 280-240-nm spectral region. The last data are consistent with the existence of an inherently chiral chromophore due to the mutual dissymmetric disposition of the two dehydro-Phe residues. On these bases it is hypothesized that doubly unsaturated peptides have in solution a rigidly fixed conformation probably stabilized by intramolecular hydrogen bonding.
Journal of Molecular Structure, 2016
The present communication deals with the eco-friendly synthesis, spectral properties and X-ray crystal structure of an indole derivative-Ethyl 2'-amino-3'-cyano-6'-methyl-5-nitro-2-oxospiro [indoline-3,4'-pyran]-5'-carboxylate. The title compound was synthesized in 87% yield. The crystal structure of the molecule is stabilized by intermolecular NeH … N, NeH … O and CeH … p interactions. The molecule is organized in the crystal lattice forming sheet like structure. To interpret the experimental data, ab initio computations of the vibrational frequencies were carried out using the Gaussian 09 program followed by the full optimizations done using Density Functional Theory (DFT) at B3LYP/6-31+G(d,p) level. The combined use of experiments and computations allowed a firm assignment of the majority of observed bands for the compound. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) with frontier orbital gap were presented. The electronic and charge transfer properties have been explained on the basis of highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular orbitals (LUMOs) and density of states (DOS). From the optimized geometry of the molecule, molecular electrostatic potential (MEP) distribution, frontier molecular orbitals (FMOs) of the title compound have been calculated in the ground state theoretically. The theoretical results showed good agreement with the experimental values. First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compound.
The Journal of Physical Chemistry B, 2003
We have measured the band profile of amide I in the infrared, isotropic, and anisotropic Raman spectra of cationic L-alanyl-D-alanyl-L-alanine, L-lysyl-L-alanine-L-alanine, and L-seryl-L-alanine-L-alanine in D 2 O. Additionally, we recorded spectra of N-acetyl-L-alanyl-L-alanine in D 2 O and in DMSO-d 6 . The respective intensity ratios of the two amide I bands depend on excitonic coupling between the amide I modes of the two peptides. These intensity ratios were obtained from a spectral decomposition and then used to determine the dihedral angles between the peptide groups by means of a recently developed algorithm (Schweitzer-Stenner, Biophys. J., 83, 83, 523, 2002). The validity of the obtained structures was checked by measuring the vibrational circular dichroism of the amide I bands. L-Lysyl-L-alanyl-L-alanine, L-seryl-L-alanyl-L-alanine, and acetyl-L-alanyl-L-alanine adopt structures similar to that observed for L-alanyl-L-alanyl-L-alanine. This suggests that the N-terminal residues do not significantly influence the dihedral angles between the two peptide groups. If one assumes a single dominant conformer, one obtains a -helix or extended polyproline II conformation, while a two-conformer model yields coexisting polyproline II and extended -type conformers. Acetyl-Lalanyl-L-alanine in DMSO-d 6 adopts a -sheet-like structure. Its amide I bands are significantly less broadened than those observed with D 2 O solvent. Our results show that hydrogen bonding between the peptide and water molecules contributes significantly to the inhomogeneous broadening of amide I bands and stabilizes the polyproline II conformation.
Journal of Taibah University for Science
In this work, the known and unknown structural as well as biological properties of 3-(2-aminoethyl) indole (tryptamine) were interpreted using molecular spectroscopy (FT-IR, FT-Raman, NMR and UV-Visible) and cheminformatic tools. The supportive drug-related information was gained by analysing the obtained data which will be useful for the drug chemist for the pharmaceutical research. The important biological properties of the present chemical species satisfied the Lipinski five rules and it was opt to fabricate complex antibiotic compounds. The acquired charge potential load for creating antibiotic strain on compositional parts was keenly observed from the obtained data and it was evaluated by the vibrational analysis and Mulliken charge profile. From the NMR data, the chemical nodal points were noted and their movement around the molecule was carefully monitored. The degenerate and non-degenerate energy profile of orbital interaction system was studied and the link of chemical reactivity path was identified. The significance of excited electronic transitions among non-bonding molecular orbital system was justified and their transitional energy coefficient was determined. The toxicity level was checked from the chirality characteristics and enantiomer structure obtained from vibrational circular dichroism profile.
Nitriles and Amidines of Optically Active Acylamino Acids and Peptides
The Journal of Organic Chemistry, 1963
mol. wt.,I6 242. Preparation of threo-Chlorohydrin I1 from cis-I.-By following the same procedure as described for trans-I, cis-I gave 84Oj, yield of threo-chlorohydrin 11, m.p. 87-88", from hydrogen chloride in benzene solution and 76% yield of 11, m.p. 87-88', from hydrogen chloride in methanol. A mixture melting point of these chlorohydrins with that from trans-I gave no depression and their infrared spectra were identical. Their elemental analyses and molecular weights were in agreement with those calculated for the desired product.
The Journal of …, 1999
We have measured the polarized nonresonance and resonance Raman as well as FTIR spectra of the model peptides glycylglycine and N-acetylglycine in H 2 O and D 2 O at pH/pD values between 1.5 and 12.0 with visible, near UV, and far UV excitation wavelengths. The spectra were self-consistently analyzed to obtain reliable spectral parameters of even strongly overlapping bands. Additionally, we have analyzed the polarized nonresonance and preresonance Raman spectra of glycylglycine single crystals. The most important result of this analysis is that for glycylglycine all amide bands as well as the symmetric carboxyl stretch band at ca. 1400 cm -1 are doublets. As shown in an earlier study (Sieler, G.; Schweitzer-Stenner, R. J. Am. Chem. Soc. 1997, 119, 1720) the amide I doublet results from vibrational coupling of the delocalized H 2 O bending mode with internal coordinates of the amide I mode. The amide III doublet is interpreted to result from vibrational coupling between the twisting mode of the C R methylene group and internal coordinates which normally give rise to the amide III vibration (i.e., CN and C R1 C stretching). In contrast, the amide II and carboxylate subbands are assigned to different conformers with respect to the torsional coordinate of the carboxylate group. While the higher frequency subband of the amide II and carboxylate bands may reflect a parallel orientation of the latter with respect to the peptide, which could be stabilized by hydrogen bonding to NH, the lower frequency band may reflect different orientations in which the carboxylate is hydrogen bonded to water. For N-acetylglycine we also observe two subbands underlying amide I and the carboxyl symmetric stretch band, which again reflects vibrational mixing with water and multiple rotational substates of the carboxylate, respectively.
Pseudo-peptides in drug discovery : A newer technology
2010
Drug discovery is devoted to the topic and draws toge ther knowledge gained on different types of peptidomimetics and other pseudo-peptides with drug prop erties. It includes peptoides (N-substituted oligoglycines) beta-peptides, gamma-peptides, pyrrole-imidazo le p lyamides, DNA-like peptide nucleic acids, Alpha-helical peptide nucleic acids, DNA-cleaving pse udo-peptides in DNA binders as well as peptide nucleic acids. Peptides are among the most versatile bioa ctive molecules, yet they do not make good drugs, because they are quickly degraded or modified in the body. Thus, drug discovery has turned to the novel field of peptidomimetics to design non-peptide compoun ds mimicking the pharmacophore and thus the activity of the original peptide. These novel compou nds open up new perspectives in drug design by providing an entire range of highly specific pharmace uti als that have a high bioavailability. Peptides ar e among the most versatile bioactive molecules, yet the do not make ...