Insertion of achiral ω-amino acids into peptide sequences results in replacement of scissile peptide bonds by proteolytically stable C−C bonds. This provides a convenient means of creating peptidomimetics. The present study establishes the preservation of helical structures in octa- and undecapeptides with centrally located β- and γ-amino acids in the sequence. X-ray diffraction analyses of single crystals and NMR studies have been used to investigate the extent of perturbations of a regular 310- or α-helix by the introduction of (−CH2−) n groups into the backbone by the use of the β-Ala-γ-Abu segment (β-Ala = β-alanine, γ-Abu = γ-aminobutyric acid), which is formally homomorphous with a (Gly)3 segment. In crystals, the octapeptide Boc-Leu-Aib-Val-β-Ala-γ-Abu-Leu-Aib-Val-OMe (1) and the undecapeptide Boc-Leu-Aib-Val-β-Ala-γ-Abu-Leu-Aib-Val-Ala-Leu-Aib-OMe (2) retain their helical motifs with minor bulges. Five new types of 4 → 1, 5 → 1, and 6 → 1 hydrogen bond rings are formed with up to three extra CH2 moieties. Cell parameters for peptide 1 are space group P212121 with a = 11.506 (1) Å, b = 16.600 (1) Å, c = 27.362(1) Å, and R = 6.1% for 2696 data measured >4σ(F); for the undecapeptide 2, the space group is P21 with a = 8.605 (3) Å, b = 22.806 (4) Å, c = 19.014 (3) Å, β = 101.47(2)°, and R = 7.5% for 3797 data measured >4σ(F). Helical conformations in solution are also maintained for peptide 2 as is evident from NMR studies in CDCl3, which suggest that the centrally positioned, flexible β-Ala-γ-Abu segment can be comfortably accommodated into helical structures adopting gauche conformations about specific C−C bonds of the poly(methylene) units. Twenty structures for backbone conformations generated from MD simulations using NMR-derived contraints, superpose with a low RMSD value (0.78 ± 0.05 Å), further indicating that in these peptides the conformational flexibility of the β-Ala-γ-Abu segment is limited and confined to largely helical conformations.

The small-sized molecules that have been developed from single hydrophobic amino acids (Phe, Trp, Tyr and Leu) by suitably protecting the -NH 2 and -CO 2 H groups generate diverse nanoscopic structures -such as nanorods, nanofi brils, nanotubes, and nanovesicles -depending upon the protection parameters and solvent polarity. The vesicular structures get disrupted in the presence of various salts, such as KCl, CaCl 2 , (NH 4 ) 2 SO 4 and N(n-Bu) 4 Br. Insertion of unnatural ( o / m / p )-aminobenzoic acids as a protecting group and the lack of conventional peptide bonds in the molecules give the nanostructures proteolytic stability. The nanostructures also show signifi cant thermal stability along with a morphological transformation upon heat treatment. Our in vitro studies reveal that the addition of micromolar concentration "curcumin" signifi cantly reduces the formation of amyloid-like fi brils. These diverse nanostructures are used as a template for fabricating silver nanoparticles on their outer surfaces as well as in the inner part, followed by calcination in air which helps to obtain a 1D silver nanostructure. Furthermore, the nanovesicles are observed to encapsulate a potent drug (curcumin) and other biologically important molecules, which could be released through salt-triggered disruption of vesicles.

A set of two modified tripeptides containing conformationally rigid m-aminobenzoic acid (m-ABA) as a template at the C-terminal self-assemble to form diverse micro-and nanostructure materials such as nanovesicles, nanotubes, giant microvesicles, macroporous vesicular structures including macroporous films, macro-and mesoporous materials, and organo gels-depending upon the solvent polarity. A balanced participation of the hydrogen bonding and the p-p interactions mainly between aromatic rings of m-ABA is crucial for this morphological diversity. Insertion of an aromatic amino acid instead of an aliphatic one in the peptide sequence drastically changes the morphology of the nanostructures formed from a particular solvent system. Interestingly these short hydrophobic peptides form saltresponsive multilayer vesicular structures from methanolic solutions, where the diameter of the vesicles increases with an increase of concentration. The most important property of these multilayer vesicular structures is the encapsulation of a potent natural hydrophobic drug curcumin and of a fluorescent dye rhodamine B, which can be effectively released in presence of biocompatible metal ions. Moreover, the encapsulation efficiency and release profile of drug and other biologically important guest molecules have been successfully quantified. We have developed a simple modified peptide based organogelator from chloroform, where the xerogel shows the striking property of adsorbing dye rhodamine B from water, which can be utilized in water purification by removing the toxic dye from waste water. Short peptide based macroporous vesicular structures including macroporous films have been successfully fabricated through controlled self-assembly employing solvents with different chloroform-petroleum ether ratios. Furthermore, the mesoporous structures prepared from toluene can efficiently absorb I 2 .

Incorporation of easily available achiral omega-amino acid residues into an oligopeptide results in substitution of amide bonds by polymethylene units of an aliphatic chain, thereby providing a convenient strategy for constructing a peptidomimetic. The central Gly-Gly segment of the helical octapeptide Boc-Leu-Aib-Val-Gly-Gly-Leu-Aib-Val-OMe(1) has been replaced by delta-amino-valeric acid (delta-Ava) residue in the newly designed peptide Boc-Leu-Aib-Val-delta-Ava-Leu-Aib-Val-OMe(2). 1H-nmr results clearly suggest that in the apolar solvent CDCl3, the delta-Ava residue is accommodated into a folded helical conformation, stabilized by successive hydrogen bonds involving the NH groups of Val(3), delta-Ava(4), and Leu(5). The delta-Ava residue must adopt a gauche-gauche-trans-gauche-gauche conformation along the central polymethylene unit of the aliphatic segment, a feature seen in an energy-minimized model conformation based on nmr parameters. The absence of hydrogen bonding functionalities, however, limits the elongation of the helix. In fact, in CDCl3, the folded conformation consists of an N-terminal helix spanning residues 1-4, followed by a Type II beta-turn at residues 5 and 6, whereas in strongly solvating media like (CD3)2SO, the unfolding of the N-terminal helix results in beta-turn conformations at Leu(1)-Aib(2). The Type II beta-turn at the Leu(5)-Aib(6) segment remains intact even in (CD3)2SO.CD comparisons of peptides 1 and 2 reveal a "nonhelical" spectrum for 2 in 2,2,2-trifluoroethanol.

The Schellman motif is a widely observed, helix terminating structural motif in proteins, which is achieved by the adoption of a left-handed helical (R L ) conformation by a C-terminus residue. The resulting hydrogen bonding pattern involves an intramolecular 6 f 1 interaction. This helix terminating motif is readily mimicked in synthetic helical peptides by placing an achiral residue at the penultimate position of the helix. The crystal structure of the heptapeptide Boc-Leu-Aib-Val-Gly-Leu-Aib-Val-OMe (1) reveals a 3 10 -helix terminated by a Schellman motif with Aib (6) adopting an R L -conformation. The crystals are in the space group P2 1 with a ) 9.958(3)Å, b ) 20.447-(3)Å, c ) 11.723 (2)Å, ) 99.74(2)°, and Z ) 2. The final R 1 and wR 2 values are 7.2% and 18.9%, respectively, for 1731 observed reflections [I g 2σ(I)]. A 6 f 1 hydrogen bond between Aib(2)CO----Val(7)NH and a 5 f 2 hydrogen bond between Val(3)CO----Aib(6)NH are observed. An analysis of several R L terminated helical peptides in crystals suggests that the medium range)] interproton distances are indeed characteristic of the Schellman motif. NMR studies in CDCl 3 establish retention of the 3 10 -helical conformation with key NOEs demonstrating the persistence of the conformation determined in crystals. The present study demonstrates the identification of the Schellman motif in solution in a synthetic helical peptide.