Darshan Ranganathan

Design and synthesis of AB3-type (A = 1,3,5-benzenetricarbonyl unit; B = Glu diOME or Glu7 octa OMe) peptide dendrimers: Crystal structure of the first generation†‡

The first generation molecule of glutamic acid-based dendrons on a 1, 3,5-benzenetricarbonyl core leads to a cylindrical assembly as demonstrated by single crystal x-ray diffraction. The benzene pi-pi stack (A) is stabilized by vertical NH...O===C hydrogen bonding with each subunit participating in three intermolecular hydrogen bonds related by three-fold rotation symmetry.

Protein-associated pigments that accumulate in the brunescent eye lens: Identification of a quinoline derivative

Brunescent (dark brown) cataract is particularly prevalent in the tropics. Enzymatic digestion of the insoluble protein fraction of brunescent cataractous eye lenses from India, followed by high performance liquid chromatographic separation of the pigments and spectroscopic investigations, have led to the identification of one of the pigments as 4‐hydroxyquinoline‐3‐[α‐aminoacetic acid] (compound A). The 4‐hydroxyquinoline moiety is shown to be a photodynamic agent that generates O•− 2 and leads to protein crosslinking. This suggests that the compound A may play a long‐term deleterious role in situ in the lens.

SYNTHESIS OF TOTALLY CHIRAL, MULTIPLE ARMED, POLY GLU AND POLY ASP SCAFFOLDINGS ON BIFUNCTIONAL ADAMANTANE CORE

Abstract Three successive generations of peptidic scaffoldings consisting of two, six and fourteen chiral (all L) centres and four, eight and sixteen carbomethoxy groups, respectively, at the periphery with adamantane nucleus as the central core have been constructed by linking the two halves of corresponding Asp/Glu dendrons by 1,3 - bifunctional adamantane unit. Energy minimization and 1H NMR studies have shown these scaffoldings to adopt increasingly globular and compact architecture with each succeeding generation.

Design of a chemical nuclease model with (Lys)2Cu as the core motif

Coded amino acid L-lysine is utilized for the design of a chemical nuclease model wherein the α-amino carboxylate unit of the amino acid is used for the formation of the copper complex acting as the metal cleaving centre, and the ω-amino function of the molecule is exploited to carry the DNA recognition elements; models with duplex purines and quinazolines as the carrier ligands attached at the ω-amino end of the lysine–metal template are synthesized and demonstrated to effect the cleavage of double stranded DNA under physiological conditions.

Oxalopeptides as core motifs for protein design

Oxalopeptides are demonstrated to be useful core motifs for bi-directional chain elongation leading to peptide homologues with interesting folding behaviour, thus constituting a useful strategy for protein backbone modification.

Designer cyclopeptides for self-assembled tubular structures

A simple design strategy for a facile and direct entry into hydrogen-bonded peptide nanotubes is delineated with polymethylene-bridged cystine-based macrocycles. The key feature of the design is the placement of a pair of self-complementary hydrogen-bonding (NH–CO or NH–CO–NH) groups at almost opposite poles of the ring. A large variety of cyclobisamides and bisureas prepared in a single step by direct condensation of commercially available 1,ω-alkane dicarbonyl dichloride or diisocyanate with either cystine diOMe or its extended bispeptide were examined by X-ray crystallography and shown to possess an inherent property of self-assembling into hydrogen-bonded, open-ended, hollow tubular structures. The totally hydrophobic interior of the cyclobisamide tubes creates a micro environment capable of solubilizing highly lipophilic substances in water. The cyclic bisurea tubes are demonstrated to act as excellent receptors for selective binding to 1,ω-alkane dicarboxylates. The scope of the design is extended to the creation of tubular structures by stacking of rings through aromatic π-π interactions.

Self-assembling urea-based peptidomimetics: A simple one-step synthesis and crystal structure of Core β-alanyl ureylene retro-bispeptides (MeOAaa[NHCONH]CH2CH2CONHAaaOMe; Aaa = amino acid A)

A novel family of urea-based peptidomimetics containing β-alanyl unit at the core has been synthesized by a simple one-step procedure. Solid state structures of some representative examples have shown self-assembly into highly ordered, extended hydrogen-bonded chains and ribbons with modest NLO activity.

Design, synthesis and membrane ion transport properties of cystine- and serine-based cyclo-4-oxa-heptane-1,7-bisamides

Abstract A new class of cyclobisamides, having the general profile of amino acid (cystine or serine)–ether composites, as potentially efficient ion transporters has been designed and synthesized. In model membranes, the adamantane harboring composites exhibited 57–66% of gramicidin A activity in ion transport.

Cystine-based cyclic oligoureas: a new class of hydrogen-bonding electroneutral anion receptors

Cystine-based symmetrical cyclic oligoureas, synthesized in a one-pot reaction from L-cystine dimethyl ester and triphosgene, are demonstrated to act as versatile neutral receptors for both inorganic and organic anions operating exclusively through hydrogen bonds; 1H NMR studies have shown that while the cyclic triurea prefers to complex with spherical (halides) and trigonal planar (nitrate) anions, the higher oligomer tetraurea can trap the tetragonal planar squarate dianion with modest efficiency.

Diamond crowns: Design, synthesis and X-ray crystallographic studies of a novel family of adamantane-containing crown ethers

A novel family of crown ethers, containing adamantane units in the cyclic framework, has been designed and synthesized by a straightforward one-step procedure. The design strategy permits the incorporation of a variety of α-amino acids to provide adamantane-constrained chiral crown ethers for use as simple models in studying ion-transport and host-guest complexation. X-ray crystallographic studies on four members of this family have revealed interesting conformational features. Ion complexation studies of several members with alkali metal and ammonium ions are reported.