Pulmonary hypertension alters natural history of anomalous left coronary artery.

A girl who was diagnosed at 8 months old with anomalous left coronary artery from the pulmonary artery and was subsequently lost to follow-up, presented at the age of 11 years with congestive heart failure and severe mitral regurgitation with supra-systemic pulmonary artery pressure. With progressive mitral regurgitation, coronary steal is reduced by the rising pulmonary artery pressure, and patients present late with severe valvular cardiomyopathy.

Holt-oram syndrome with hemizygous continuation of inferior vena cava.

A rare and previously unreported combination of Holt-Oram syndrome, atrial septal defect, patent ductus arteriosus, isolated left atrial isomerism and inferior vena caval interruption with hemizygous continuation to the left superior vena cava is described.

Late entrapment of ball and cage valve in mitral position.

A 32-year-old female underwent mitral valve replacement with total chordal preservation (Miki's technique) using 26 mm (1M) Starr-Edward prosthesis (SEP) in 1988. The patient was in NYHA class-I until 2001. She progressed to NYHA class-III with paroxysmal nocturnal dyspnoea. Transthoracic echocardiogram showed increased prosthetic valve gradient, and cardiac catheterization confirmed the findings. Intraoperatively, the poppet movement in the cage was found to be restricted due to the preserved subvalvular apparatus entrapping the poppet inside the prosthetic valve cage.

One-and-a-half ventricle repair for right ventricular endomyocardial fibrosis.

One-and-a-half ventricle repair, consisting of endocardiectomy with tricuspid valve replacement and bidirectional cavopulmonary shunt, was performed on a patient with right ventricular endomyocardial fibrosis and right ventricular outflow tract obstruction. The patient made a smooth recovery. We believe that this repair provides good palliation for a subset of patients with right ventricular endomyocardial fibrosis.

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. The difference in the handedness of left and right arms is reflected in the self-assembly patterns. Thus, while the NBE(Aib(4))(2) molecule self-assembles to form an infinite hydrogen-bonded superhelical ladder, the Janus molecule NBE(Aib(5))(2) crystallizes as individual units surrounded by water molecules. The structures of Z-Aib(4)-OMe and Z-Aib(5)-OMe are also presented to compare their conformations with the helical arms of the title compound and also to the already known structures of other X-Aib(n) -Y compounds. The helices in all the molecules are the 3(10)-type.

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...O===C hydrogen bonding with each subunit participating in three intermolecular hydrogen bonds related by three-fold rotation symmetry.

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. This novel class of constrained cyclic peptides are demonstrated to adopt beta-sheet- or hairpin-like conformation as shown by (1)H NMR and CD spectra. Membrane ion-transport studies have shown that the norborneno cyclic peptides 4b and 7b containing Leu-Leu or Val-Val pendants symmetrically placed on the exterior of the ring show high efficiency and selectivity in the transport of specifically monovalent cations. This property can be attributed to the hairpin-like architecture induced by the norbornene unit since the bis-adamantano peptide 15 containing two pairs of Leu-Leu pendants on the exterior is able to transport both monovalent (Na(+), K(+)) and divalent (Mg(2+)/Ca(2+)) cations.

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...N hydrogen bond for all the members. Whereas the Aib3 segment in Py(Aib3)2 showed only the onset of a 3(10)-helical structure, the presence of a well-formed 3(10)-helix in both Aib4 arms of Py(Aib4)2 was evident in the 1H NMR of the bispeptide. X-ray crystallographic studies have shown that in the solid state, whereas Py(Aib2)2 molecules organize into a sheet-like structure and Py(Aib3)2 molecules form a double-stranded string assembly, the tetra Aib bispeptide, Py(Aib4)2, is organized to form a tetrameric assembly which in turn extends into a continuous channel-like structure. The channel is totally hydrophobic in the interior and can selectively encapsulate lipophilic ester (CH3COOR, R=C2H5, C5H11) molecules, as shown by the crystal structures of the encapsulating channel. The crystal structure parameters are: 1b, Py(Aib2)2, C25H37N5O8, sp. gr. P2(1)2(1)2(1), a=9.170(1) A, b=16.215(2) A, c=20.091(3) A, R=4.80; 1c, Py(Aib3)2, C33H51N7O10H2O, sp. gr. P1, a=11.040(1) A, b=12.367(1) A, c=16.959(1) A, alpha =102.41 degrees, beta =97.29 degrees, gamma =110.83 degrees, R1=6.94; 1 da, Py(Aib4)2.et ac, C41H65N9O12.1.5H2O.C4H8O2, sp. gr. P1, a=16.064(4) A, b=16.156 A, c=21.655(5) A, alpha =90.14(1)degrees, beta=101.38(2) degrees, gamma=97.07(1)degrees, Z=4, R1=9.03; 1db, Py(Aib4)2.amylac, C41H65N9O12.H2O.C7H14O2, P2(1)/c, a=16.890(1) A, b=17.523(1)A, c=20.411(1) A, beta=98.18 degrees, Z=4, R=11.1 (with disorder).

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. A noteworthy feature of the strategy is the formation of the 1 + 1 + 1 + 1 catenane arising from the interlocking of sebacoyl-bridged tyrosine rings. The potential of tyrosinophanes to serve as simple aromatic hosts in the study of pi-cation type interactions was illustrated with Pyr-bridged macrocycles (6b-8b) using N-methylacridinium hexafluorophosphate as the pyridinium guest. The K(assoc) value with 6b was found to be 8.95 x 10(3) M(-)(1).

Self-assembling bis-dendritic peptides: design, synthesis and characterization of oxalyl-linked bis-glutamyl peptides [Glu(n)(CO2Me)n + 1-CO-]2; n = 1,3,7.

Three generations of glutamic acid dendrons [Glu(n),(CO2Me)n + 1; n = 1, 3, 7] have been joined together head-to-head by an oxalyl unit to form highly sterically congested bis-Glu-dendritic peptides with gelling properties. The single crystal X-ray structure of the first generation bis-dendritic peptide showed an extended hydrogen-bonded chiral tape with modest nonlinear optical activity.