Can a consecutive double turn conformation be considered as a peptide based molecular scaffold for supramolecular helix in the solid state?

Helices and sheets are ubiquitous in nature. However, there are also some examples of self-assembling molecules forming supramolecular helices and sheets in unnatural systems. Unlike supramolecular sheets there are a very few examples of peptide sub-units that can be used to construct supramolecular helical architectures using the backbone hydrogen bonding functionalities of peptides. In this report we describe the design and synthesis of two single turn/bend forming peptides (Boc-Phe-Aib-Ile-OMe 1 and Boc-Ala-Leu-Aib-OMe 2) (Aib: alpha-aminoisobutyric acid) and a series of double-turn forming peptides (Boc-Phe-Aib-IIe-Aib-OMe 3, Boc-Leu-Aib-Gly-Aib-OMe 4 and Boc-gamma-Abu-Aib-Leu-Aib-OMe 5) (gamma-Abu: gamma-aminobutyric acid). It has been found that, in crystals, on self-assembly, single turn/bend forming peptides form either a supramolecular sheet (peptide 1) or a supramolecular helix (peptide 2). unlike self-associating double turn forming peptides, which have only the option of forming supramolecular helical assemblages. (c) 2005 Elsevier Ltd. All rights reserved.

A new molecular scaffold for the formation of supramolecular peptide double helices: the crystallographic insight

A series of water-soluble synthetic dipeptides (1-3) with an N-terminally located beta-alanine residue, beta-alanyl-L-valine (1), beta-alanyl-L-isoleucine (2), and beta-alanyl-L-phenylalanine (3, form hydrogen-bonded supramolecular double helices with a pitch length of 1 nm, whereas the C-terminally positioned beta-alanine containing dipeptide (4), L-phenylalanyl-beta-alanine, does not form a supramolecular double helical structure. beta-Ala-Xaa (Xaa = Val/Ile/Phe) can be regarded as a new motif for the formation of supramolecular double helical structures in the solid state.

Anion directed template synthesis of Cu(II) complexes of a N,N,O donor mono-condensed Schiff base ligand: A molecular scaffold forming highly ordered H-bonded rectangular grids

Anion directed, template syntheses of two dinuclear copper(II) complexes of mono-condensed Schiff base ligand Hdipn (4-[(3-aminopentylimino)-methyl]-benzene-1,3-diol) involving 2,4- dihydroxybenzaldehyde and 1,3-diaminopentane were realized in the presence of bridging azide and acetate anions. Both complexes, [Cu-2(dipn)(2)(N-3)(2)] (1) and [Cu-2(dip(n))(2)(OAc)(2)] (2) have been characterized by X-ray crystallography. The two mononuclear units are joined together by basal-apical, double end-on azido bridges in complex 1 and by basal-apical, double mono-atomic acetate oxygen-bridges in 2. Both complexes form rectangular grid-like supramolecular structures via H-bonds connecting the azide or acetate anion and the p-hydroxy group of 2,4- dihydroxybenzaldehyde. Variable-temperature (300-2 K) magnetic susceptibility measurements reveal that complex 1 has antiferromagnetic coupling (J = -2.10 cm (1)) through the azide bridge while 2 has intra-dimer ferromagnetic coupling through the acetate bridge and inter-dimer antiferromagnetic coupling through H-bonds (J = 2.85 cm (1), J' = -1.08 cm (1)). (C) 2009 Elsevier B. V. All rights reserved.

Ribonucleocapsid formation of severe acute respiratory syndrome coronavirus through molecular action of the N-terminal domain of N protein

Conserved among all coronaviruses are four structural proteins: the matrix (M), small envelope (E), and spike (S) proteins that are embedded in the viral membrane and the nucleocapsid phosphoprotein (N), which exists in a ribonucleoprotein complex in the lumen. The N-terminal domain of coronaviral N proteins (N-NTD) provides a scaffold for RNA binding, while the C-terminal domain (N-CTD) mainly acts as oligomerization modules during assembly. The C terminus of the N protein anchors it to the viral membrane by associating with M protein. We characterized the structures of N-NTD from severe acute respiratory syndrome coronavirus (SARS-CoV) in two crystal forms, at 1.17 A (monoclinic) and at 1.85 A (cubic), respectively, resolved by molecular replacement using the homologous avian infectious bronchitis virus (IBV) structure. Flexible loops in the solution structure of SARS-CoV N-NTD are now shown to be well ordered around the beta-sheet core. The functionally important positively charged beta-hairpin protrudes out of the core, is oriented similarly to that in the IBV N-NTD, and is involved in crystal packing in the monoclinic form. In the cubic form, the monomers form trimeric units that stack in a helical array. Comparison of crystal packing of SARS-CoV and IBV N-NTDs suggests a common mode of RNA recognition, but they probably associate differently in vivo during the formation of the ribonucleoprotein complex. Electrostatic potential distribution on the surface of homology models of related coronaviral N-NTDs suggests that they use different modes of both RNA recognition and oligomeric assembly, perhaps explaining why their nucleocapsids have different morphologies.

Molecular archaeology of Flaviviridae untranslated regions: duplicated RNA structures in the replication enhancer of flaviviruses and pestiviruses emerged via convergent evolution.

RNA secondary structures in the 3'untranslated regions (3'UTR) of the viruses of the family Flaviviridae, previously identified as essential (promoters) or beneficial (enhancers) for replication, have been analysed. Duplicated enhancer elements are revealed as a global feature in the evolution of the 3'UTR of distantly related viruses within the genera Flavivirus and Pestivirus. For the flaviviruses, duplicated structures occur in the 3'UTR of all four distantly related ecological virus subgroups (tick-borne, mosquito-borne, no known vector and insect-specific flaviviruses (ISFV). RNA structural differences distinguish tick-borne flaviviruses with discrete pathogenetic characteristics. For Aedes- and Culex-associated ISFV, secondary RNA structures with different conformations display numerous short ssRNA direct repeats, exposed as loops and bulges. Long quadruplicate regions comprise almost the entire 3'UTR of Culex-associated ISFV. Extended duplicated sequence and associated RNA structures were also discovered in the 3'UTR of pestiviruses. In both the Flavivirus and Pestivirus genera, duplicated RNA structures were localized to the enhancer regions of the 3'UTR suggesting an adaptive role predominantly in wild-type viruses. We propose sequence reiteration might act as a scaffold for dimerization of proteins involved in assembly of viral replicase complexes. Numerous nucleotide repeats exposed as loops/bulges might also interfere with host immune responses acting as a molecular sponge to sequester key host proteins or microRNAs.