Design, Synthesis, and Characterization of Tyrosinophanes, a Novel Family of Aromatic-Bridged Tyrosine-Based Cyclodepsipeptides.

A simple two-step design strategy has been developed for the synthesis of a large variety of a new class of tyrosine-based aromatic (Ph or Pyr) bridged cyclodepsipeptides (tyrosinophanes). The design is flexible with respect to the size of the ring and the nature of the bridging unit and permits the incorporation of a variety of amino acid residues inside or outside or both inside and outside the ring as illustrated here with the preparation of tyrosine-based macrocycles with aromatic (Ph or Pyr), cage-like alicyclic (adamantane) or simple polymethylene bridging units in ring sizes varying from 26-membered to 78-membered and containing leucine residues as part of the ring or as pendants on the exterior or both inside and outside the macrocyclic ring. (1)H NMR, FT-IR, and CD studies have indicated open-ring structures for these macrocycles.

Channel-forming, self-assembling, bishelical amphiphilic peptides: design, synthesis and crystal structure of Py(Aibn)2, n=2,3,4.

The design, synthesis, characterization and self-assembling properties of a new class of amphiphilic peptides, constructed from a bifunctional polar core attached to totally hydrophobic arms, are presented. The first series of this class, represented by the general structure Py(Aibn)2 (Py=2,6-pyridine dicarbonyl unit; Aib=alpha, alpha'-dimethyl glycine; n=1-4), is prepared in a single step by the condensation of commercially available 2,6-pyridine dicarbonyl dichloride with the methyl ester of homo oligoAib peptide (Aibn-OMe) in the presence of triethyl amine. 1H NMR VT and ROESY studies indicated the presence of a common structural feature of 2-fold symmetry and an NH.

Design and synthesis of AB(3)-type (A = 1,3,5-benzenetricarbonyl unit; B = Glu diOME or Glu(7) 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..

Design, synthesis, and crystal structure of self-assembling norbornene (NBE)-supported two-helix bundles: a unique example of Janus helicity in the solid-state structure of NBE(Aib(5))(2).

Norbornene-supported bis-helical peptides with the general structure NBE(Aib(n) )(2) (NBE: 2,3-trans-norbornene dicarbonyl unit; Aib: alpha,alpha'-dimethyl glycine unit; n = 4,5) have been synthesized and examined for self-assembly preferences in the solid state. An x-ray study has revealed a phenomenon of Janus helicity in the solid state structure of NBE(Aib(5))(2). The lower homologue NBE(Aib(4))(2), however, shows an identical screw sense for both the helical arms.

Norbornene-constrained cyclic peptides with hairpin architecture: design, synthesis, conformation, and membrane ion transport.

A novel family of hairpin cyclic peptides has been designed on the basis of the use of norbornene units as the bridging ligands. The design is flexible with respect to the choice of an amino acid, the ring size, and the nature of the second bridging ligand as illustrated here with the preparation of a large number of norborneno cyclic peptides containing a variety of amino acids in ring sizes varying from 12- to 29-membered, with the choice of the second bridging ligand being a rigid norbornene (11, 13a,b), an adamantane unit (7a,b and 8), or a flexible cystine residue (4a,b and 10). The presence of built-in handles (as protected COOH groups) permits the attachment of a variety of subunits as shown here with the ligation of Leu-Leu, Val-Val, or Aib-Aib pendants in 4b, 7b, and 13b, respectively.