Conformational behavior of polyalanine peptides with and without protecting groups of varying chain lengths: population of PP-II structure!

Oculopharyngeal muscular dystrophy (OPMD), a polyalanine myopathy, occurs due to expansion of homo-polyalanine stretch in normal polyadenylating binding protein nuclear 1 (PABPN1) protein from Ala10 to Ala11-17. Therefore, the conformational behavior of polyalanine peptides with n = 10-17, with and without terminal protecting groups, have been investigated with different starting geometries in water by molecular dynamics simulation studies. Alanine peptides are shown to give rise to unordered structure irrespective of starting geometry and not more than two residues at a stretch have the same/similar set of φ, ψ values.

Conformational behavior of phenylglycines and hydroxyphenylglycines and non-planarity of phenyl rings.

The non-proteinogenic amino acids--phenylglycine (PG) and hydroxyphenylglycine (HPG) are crucial components of certain peptidic natural products and are important for the preparation of various medicines. In this, study, the conformation of model dipeptides Ac-X-NHMe of PG, p-HPG and 3, 5-di-hydroxyphenylglycine (3, 5-DHPG) was studied both in R and S form by quantum mechanical (QM) and molecular dynamics approaches. On the energy scale, the conformational states of these molecules in both the R and S were found to be degenerate by QM studies, stabilized by non-covalent interactions like carbonyl--carbonyl interactions, carbonyl-lp .

Construction and conformational behavior of peptoids with cis-amide bond geometry: design of a peptoid with alternate φ, ψ values of inverse PP-II/PP-II and PP-I structures.

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.

Conformational study of N-methylated alanine peptides and design of Abeta inhibitor.

N-Methylation increases the proteolytic stability of peptides and leads to improved pharmacological and increased nematicidal property against plant pathogens. In this study, the quantum mechanical and molecular dynamic simulation approaches were used to investigate conformational behavior of peptides containing only N-methylated alanine (NMeAla) residues and N-methylated alanine and alanine residues at alternate positions. The amide bond geometry was found to be trans and the poly NMeAla peptides were shown to populate in the helical structure without hydrogen bond with phi, psi values of - 0, 90 degrees stabilized by carbonyl-carbonyl interactions.

Insights on the structural characteristics of Vim-TBS (58-81) peptide for future applications as a cell penetrating peptide.

The plasma membrane presents a remarkable barrier for the delivery of peptide and nucleic acid based drugs to the inside of cells. This restraint in the path of their development as therapeutic agents can be offset by their conjugation to cell penetrating peptides (CPPs) that can lead to an improved pharmacological profile. In this context, conformational behavior of Vimentin Tubulin Binding Site (TBS) peptide, Vim-TBS (58-81), was investigated for its acknowledged cell penetrating properties along with Trans-activating Tat (48-60) peptide and a pro-apoptogenic peptide of p21/WAFI protein (p10).

Conformational study of poly-DeltaAbu peptides and construction of amphipathic nanostructure.

Generally, it is believed that alpha,beta-dehydroamino acid residues are most stable in the Z- form rather than in the E- form. In this study, it has been shown that poly-DeltaAbu exists in alternate Delta(E)Abu and Delta(Z)Abu form, with phi, psi values of approximately 0 degrees , 80 degrees and 35 degrees , 27 degrees for the E- and Z- forms, respectively, rather than the all Z- form. The conformational results for the peptides Ac-DeltaAbu(2)-NHMe and Ac-L/D-Ile-Delta(Z)Abu/Delta(E)Abu-NHMe suggest the incorporation of DeltaAbu in both the Z- and E- forms, which is consistent with the available observations in natural systems.

The Alzheimer beta-amyloid (Abeta(1-39)) dimer in an implicit solvent.

Oligomers of Abeta peptides are suspected as the underlying cause of Alzheimer disease. Knowledge of their structural properties could therefore lead to a deeper understanding of the mechanism behind the outbreak of this disease. As a step in this direction we have studied Abeta dimers by all-atom molecular dynamics simulations.

New type of helix and 2(7) ribbon structure formation in poly DeltaLeu peptides: construction of a single-handed template.

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.

Construction and design of single stranded collagen-like structure.

Polytheonamide B, a 48 residue long highly cytotoxic polypeptide extracted from marine sponges contains amino acids of alternate chirality and the N-terminal region is rich in t-Leu residues. The aim of this study is to analyze the effect of these alternate chiralities and conformational behavior of various model peptides containing t-Leu, in order to explore their role in designing bioactive peptides that shall offer advantages comparable to polytheonamide B, while circumventing its limitations. The conformational behavior of various peptides constructed from t-Leu of the form Ac-(L/D-X-L/D-Y)n-NHMe, where X = Gly/Ala/Leu and Y = t-Leu has been studied and compared with the corresponding peptides containing Leu residue.

Conformation of peptides constructed from achiral amino acid residues Aib and DeltaZPhe: computational study of the effect of L/D- Leu at terminal positions.

Conformational studies of the peptides constructed from achiral amino acid residues Aib and Delta(Z)Phe (I) Ac-Aib-Delta(Z)Phe-NHMe (II), and Ac-(Aib-Delta(Z)Phe)(3)-NHMe; peptides III-VI having L-Leu or D-Leu at either the N- or the C-terminal position and of peptides VII-X having Leu residues in different enantiomeric combinations at both the N- and the C-terminal positions in peptide II have been studied to design the peptide with the required helical sense. Peptide II, as expected, adopts degenerate left- and right-handed helical structures. It has been shown that the peptides IV and VI having D-Leu at either the N or the C terminus can be realized in the right-handed helical structure with the phi,psi values of -20 degrees and -60 degrees for the Aib/Delta(Z)Phe residues.

Effect of terminal achiral and chiral residues on the conformational behaviour of poly Δ(z)Phe and analysis of various interactions.

Conformational properties of the peptides containing (Δ(Z)Phe)6 with achiral (ΔAla, Gly) and chiral (Ala, Leu) residues at both the N- and C-terminal positions have been studied with a view to design a peptide with desired helical screw sense. In all the peptides, the lowest energy conformational state corresponds to Φ = 0° and Ψ = + 90° or - 90° or both +/- 90°. These structures are characterized by rise per residue of 1.