alpha,beta-Dehydroamino acid residues due to the presence of Calpha = Cbeta double bond influences the main chain and the side chain conformations. These residues have interesting chemical features including the increased resistance to enzymatic degradation. The chain length dependent conformational behavior of poly alpha,beta-dehydroleucine (DeltaLeu) peptides in both the pure forms Z and E and their various combinations like alternate ZE/EZ etc. have been investigated by using quantum mechanical method PCILO (perturbative configuration interaction of localized orbitals). The conformational states in alternate Z and E forms, with Phi, Psi values of -10 degrees , 105 degrees /1 degrees , -88 degrees for Z form and 35 degrees , 22 degrees /-34 degrees , -27 degrees for the E form are found to be the most stable and degenerate than the states in pure Z and E forms and the EZ form etc. The repeated Phi, Psi values give rise to altogether new types of left and right handed helices, and their stability increases with increasing chain length. These structures are stabilized by intramolecular hydrogen bonding, carbonyl-carbonyl interactions and hydrophobic interactions between the side chains of DeltaZLeu and DeltaELeu residues. The 2(7) ribbon structure (seven-membered hydrogen-bonded ring involving two consecutive amino acid residues) is found to be most stable and degenerate in the pentapeptide Ac-DeltaELeu5-NHMe, due to the formation of maximum hydrogen bonds. A right-handed template from achiral DeltaLeu peptides has been achieved by incorporating L-Leu at the C-terminal or D-Leu at the N-terminal.

In peptoids due to the absence of amide protons, the backbone is devoid of hydrogen bond donor, linked by tertiary amide, which can be iso-energetic between cis and trans-amide bond geometry. The peptoids can be realized with cis amide bond if the side chain of ith residue can engage the carbonyl group of ith-1 residue in CH--O interactions. Simulations studies both in water and DMSO have been carried out. The peptoid Ac-(N(tle))(7) -NMe(2) can adopt degenerate conformations with alternate φ, ψ values of inverse PP-I and PP-I type structure's, or vice versa in water. In DMSO, Ac-(N(tle))(7)-NMe(2) also adopts inverse PP-I type structure. Like polyproline, molecule adopting a rigid structure can be used as molecular markers or spacers in biological studies.The peptoid Ac-(N(ala)-N(tle))(3)-NMe(2) with alternate trans and cis amide bond geometry for N(ala) and N(tle) residue corresponding to inverse PP-II/PP-II type and for N(tle) residue of PP-I type.

No abstract

Tubulin binding compounds are key players in orchestrating anticancer effects by modulating microtubule dynamics that in turn disrupts cell motility and promotes apoptosis. However, their clinical application is limited by high toxicity resulting from their lack of specificity for cancer cells. Consequently, identifying microtubule interacting agents that demonstrate higher specificity for tumor cells continues to be a key objective in the search for more effective cancer treatments. In this context, small tubulin binding peptides (22-35 amino acids) from some intermediate filaments (IFs) were reported to bind unassembled tubulin and disrupt microtubules. To date there are no structural studies on these peptides as it is difficult to crystallize IF proteins. To narrow this wide gap in knowledge, two such peptides corresponding to the tubulin binding sites of the IF protein Desmin were studied using molecular mechanics and molecular dynamics based techniques. This is the first report on the structural plasticity of these peptides and sheds light on the imperative role of non-covalent interactions in directing the secondary structures. These findings shall be significant in guiding and facilitating the future efforts of designing peptide based anti-mitotic drugs.

Background: To date, the use of sialic acid that are reported to be elevated during malignancy has been largely unexplored for tumor imaging. The purpose of the present study was to study the modeled stable conformers of n-acetyl neuraminic acid (Neu5Ac) and its radiolabeled conjugate (Tc-99m-Neu5Ac) through computational chemistry approach and its in-vitro bioevaluation in rat C6 cell lines. Materials and Methods: The Neu5Ac was radiolabeled with Tc-99m using stannous reduction method and the radiochemical purity of Tc-99m-Neu5Ac was determined by instant thin layer chromatography. A Cheminformatic study of Tc-99m-Neu5Ac was performed by using Marvin application of ChemAxon. Glioma cancer cells were taken to evaluate the cytotoxicity and binding efficacy of Tc-99m-Neu5Ac. Results: Cheminformatic studies exhibited that the most stable conformer of Tc-99m-Neu5Ac is 15 kcal/mol more stable energetically over least stable conformer. The radiochemical yield of Tc-99m labeled Neu5Ac was observed to be greater than 90%. Further, the radiolabeled complex (Tc-99m-Neu5Ac)exhibited specificity for C6 glioma with time and concentration dependent cytotoxicity. Conclusion: In conclusion, Tc-99m-Neu5Ac has the potential to be exploited as an in-vivo radionuclide probe for tumor imaging.