Nonthreaded Isomers of Sungsanpin and Ulleungdin Lasso Peptides Inhibit H1299 Cancer Cell Migration.

Lasso peptides are a structurally distinct class of biologically active natural products defined by their short sequences with impressively interlocked tertiary structures. Their characteristic peptide [1]rotaxane motif confers marked proteolytic and thermal resiliency, and reports on their diverse biological functions have been credited to their exceptional sequence variability. Because of these unique properties, taken together with improved technologies for their biosynthetic production, lasso peptides are emerging as a designable scaffold for peptide-based therapeutic discovery and development. Although the defined structure of lasso peptides is recognized for its remarkable properties, the role of the motif in imparting bioactivity is less understood. For example, sungsanpin and ulleungdin are natural lasso peptides that similarly exhibit encouraging cell migration inhibitory activities in A549 lung carcinoma epithelial cells, despite sharing only one-third of the sequence homology. We hypothesized that the shape of the lasso motif is beneficial for the preorganization of the conserved residues, which might be partially retained in variants lacking the threaded structure. Herein, we describe solid-phase peptide synthesis strategies to prepare acyclic, head-to-side chain (branched), and head-to-tail (macrocyclic) cyclic variants based on the sungsanpin (Sun) and ulleungdin (Uln) sequences. Proliferation assays and time-lapse cell motility imaging studies were used to evaluate the cell inhibitory properties of natural Sun compared with the synthetic Sun and Uln isomers. These studies demonstrate that the lasso motif is not a required feature to slow cancer cell migration and more generally show that these nonthreaded isomers can retain similar activity to the natural lasso peptide despite the differences in their overall structures.

Rational construction of triazole/urea based peptidomimetic macrocycles as pseudocyclo-ß-peptides and studies on their chirality controlled self-assembly.

A tandem macro-dimerization reaction via a Cu(I) catalyzed azide/alkyne cycloaddition reaction has been employed to construct triazole/urea based peptidomimetic macrocycles considered as pseudocyclo-ß-peptides. Introduction of one particular chirality in the peptide backbone can alter the conformation as well as nature of self-assembly from cyclic D-,L-,α-peptide to cyclo-ß-peptide. One of them (16a) forms antiparallel dimers while the other (16b) undergoes higher order aggregation to form a nanorod structure.

Design and synthesis of regioisomeric triazole based peptidomimetic macrocycles and their dipole moment controlled self-assembly.

Two peptidomimetic macrocycles, regioisomeric in terms of the position of triazole/amide, have been synthesized. Both undergo self-assembly in a parallel manner but in solvents of opposite polarity, ascribed to (ß, ß) and (ß-D, ß-L) hydrogen bonding leading to formation of two different unique classes of organic nanostructures.

Dynamics of pest and its predator model with disease in the pest and optimal use of pesticide.

In this paper, we propose and analyze a prey-predator system. Here the prey population is taken as pest and the predators are those eat the pests. Moreover we assume that the prey species is infected with a viral disease forming into susceptible and infected classes and infected prey is more vulnerable to predation by the predator. The dynamical behavior of this system both analytically and numerically is investigated from the point of view of stability and bifurcation. Then we explicitly introduce a control variable for pest control into the analysis by considering the associated control cost. In the nonconstant control case, we use Pontrygin's Maximum principle to derive necessary conditions for the optimal control of the pest. Then we demonstrated the analytical results by numerical analysis and characterized the effects of the parameter values on optimal strategy.

Simultaneous parallel and antiparallel self-assembly in a triazole/amide macrocycle conformationally homologous to D-,L-α-amino acid based cyclic peptides: NMR and molecular modeling study.

A 1,4-linked triazole/amide based peptidomimetic macrocycle, synthesized from a triazole amide oligomer of cis-furanoid sugar triazole amino acids, possesses a conformation resembling the D-,L-α-amino acid based cyclic peptides despite having uniform backbone chirality. It undergoes a unique mode of self-assembly through an antiparallel backbone to backbone intermolecular H-bonding involving amide NH and triazole N2/N3 as well as parallel stacking via amide NH and carbonyl oxygen H-bonding, leading to the formation of a tubular nanostructure.