Biomedical subjects

E Ozeki

Publications and source records attributed to E Ozeki.

8 recordsLinked to original sources

PubMed1989

Ca2+ binding cyclic octapeptides having an alternating Sar and a hydrophobic amino acid in the sequence.

Cyclic octapeptides having alternating Sar and hydrophobic amino acid sequences, such as cyclo[Lys(Z)-Sar-Leu-Sar-Leu-Sar-Leu-Sar] (C8KL), cyclo[Glu(OMe)-Sar-Lys(Z)-Sar-Leu-Sar-Leu-Sar] (C8KE, and cyclo[Lys(Suc)-Sar-Leu-Sar-Leu-Sar-Leu-Sar] [C8K(Suc)L, Suc represents succinic acid], were synthesized. These cyclic octapeptides formed a complex selectively with Ca2+. Upon complexation, trans peptide bonds of Sar residues were isomerized to cis peptide bonds. C8KL and C8KE showed very similar characteristics of Ca2+ binding, extraction of Ca2+ from an aqueous solution to a chloroform solution, and Ca2+ transport through a liquid chloroform membrane. C8KL transported Ca2+ across the lipid bilayer membrane above the phase-transition temperature, while C8KE and C8K(Suc)L did not. Therefore, the transport of Ca2+ through the lipid bilayer membrane is very sensitive to the hydrophobicity of the carrier molecule.

Amino Acid Sequence↗

PubMed1989

Ca2+ transport through lipid membrane by diastereomer cyclic octapeptides.

Effects of the nature and orientation of a side chain in cyclic octapeptides on Ca2+ transport were examined by using cyclo[L-Lys(Z)-Sar-L-Leu-Sar]2 (C8-L), cyclo[L-Lys(Z)-Sar]4 (C8KS), and their diastereomer cyclic octapeptides, cyclo[L-Lys(Z)-Sar-D-Leu-Sar]2 (C8-D) and cyclo[L-Lys(Z)-Sar-D-Lys(Z)-Sar]2 (C8Kk). All these cyclic octapeptides were found to take a single conformation in CDCl3, and the conformation was C2-symmetric for C8-L and C8-D, and C4-symmetric for C8KS and C8Kk. They formed a complex with Ca2+. Upon complexation, C8KS accompanied isomerization of peptide bonds, but C8-D retained the arrangement of peptide bonds. The amount of Ca2+ extracted from an aqueous solution to a chloroform solution by all L cyclic octapeptide C8-L or C8KS was about twice that of Na+, but 6-8-fold smaller than that by C8-D or C8Kk including D units. These cyclic octapeptides were capable of transporting Ca2+ through a lipid membrane above the phase transition temperature, and the transport rate decreased in the order of C8Kk-C8KS greater than C8-D greater than C8-L.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1989

Synthesis and interaction with metal ions of cyclic oligopeptides bearing carboxyl groups.

Cyclic di- and tetrapeptides bearing carboxyl or carboxylate groups, cyclo[Glu(OBzl)-Glu(OMe)], cyclo[Glu-Glu(OMe)], cyclo(Glu-Glu), cyclo[Glu(OMe)-Pro)2, and cyclo(Glu-Pro)2, were synthesized and investigated on the intramolecular interaction of carboxyl side chains in the complexation with metal ions in relation with the conformation. The three kinds of cyclic dipeptides were found to take a flagpole boat conformation. Folded conformation of side chains was predominant for cyclo[Glu(OBzl)-Glu(OMe)] and cyclo[Glu-Glu(OMe)]. However, cyclo(Glu-Glu) took an unfolded conformation. Intramolecular interaction of carboxyl groups was observed neither in free state nor in complexation with metal ions. The intramolecular interaction of carboxyl groups was observed in the case of cyclo(Glu-Pro)2 in the absence of metal ions added. Cyclo[Glu(OMe)-Pro]2 and cyclo(Glu-Pro)2 formed a complex with Ca2+ and Ba2+ without participation of side chains.

Dipeptides↗

PubMed1989

Conformation and complexation with metal ions of cyclic hexapeptides: cyclo (L-Leu-L-Phe-L-Pro)2 and cyclo [L-Cys(Acm)-L-Phe-L-Pro]2.

Cyclic hexapeptides, cyclo (L-Leu-L-Phe-L-Pro)2 and cyclo[L-Cys(Acm)-L-Phe-L-Pro]2, in which Acm represents an acetoamide-methyl group, were synthesized, and the conformation and complexation with metal ions were investigated. Cooperation of the carbonyl groups of the Cys(Acm) side chains with those of the cyclic skeleton in complexation was especially examined. Cyclo(L-Leu-L-Phe-L-Pro)2, which possesses no functional groups on side chains, was taken as the reference compound. 13C- and two-dimensional n.m.r. measurements revealed that cyclo(L-Leu-L-Phe-L-Pro)2 and cyclo[L-Cys(Acm)-L-Phe-L-Pro]2 took a C2-symmetric conformation containing cis L-Phe-L-Pro bonds in chloroform and acetonitrile. Both cyclic hexapeptides were found to complex selectively with Ba2+ and Ca2+ in acetonitrile. On complexation the conformation of either cyclic hexapeptide changed into a similar one. However, the binding constant of cyclo[L-Cys(Acm)-L-Phe-L-Pro]2 was higher than that of cyclo(L-Leu-L-Phe-L-Pro)2. The n.m.r. measurements showed that the amide carbonyl groups of Cys(Acm) side chains as well as those of cyclic skeleton in cyclo[L-Cys(Acm)-L-Phe-L-Pro]2 cooperatively bound the cations.

Amino Acid Sequence↗

PubMed1989

Cyclic hexapeptides bearing carboxyl groups. Interaction with metal ions and lipid membrane.

Three cyclic hexapeptides bearing carboxyl groups, cyclo(L-Asp-L-Phe-L-Pro)2, cyclo(L-Aad-L-Phe-L-Pro)2 (Aad represents alpha-amino adipic acid residue), and cyclo(D-Asp-D-Phe-L-Pro)2 were synthesized and investigated on conformation, complexation with metal ions, and interaction with lipid membrane. These cyclic hexapeptides were found to take several different conformations, though their reference compounds, cyclo(L-Leu-L-Phe-L-Pro)2 and cyclo[D-Asp(OMe)-D-Phe-L-Pro]2, took a single C2 symmetric conformation. Cyclo(D-Asp-D-Phe-L-Pro)2 formed complexes with Ba2+ and Ca2+, whereas cyclo(L-Asp-L-Phe-L-Pro)2 and cyclo(L-Aad-L-Phe-L-Pro)2 did not. The latter two take amphiphilic structures and were distributed to lipid membrane more easily than cyclo(D-Asp-D-Phe-L-Pro)2. Cyclo(D-Asp-L-Phe-L-Pro)2 binds Ca2+ on the lipid membrane.

1,2-Dipalmitoylphosphatidylcholine↗

PubMedDate not supplied

Development of a novel biocompatibility test method based on intracellular calcium ion mobilization.

This paper presents a novel evaluation method for determining platelet/material interaction at the transmembrane level by incorporation of a Ca-sensitive fluorophore (Fura-2) into platelets. The transmembrane stimulation of platelets which are eluted from commercially available artificial dialyzers was quantitatively measured as the elevation of intracellular free calcium ion concentration. This method clearly differentiated platelet response to hydrophilic (ethylene vinyl alcohol copolymer and cellulose) vs. hydrophobic (polyacrylonitrile and cellulose acetate) membranes, and offers a versatile means to understanding platelet/material interaction.

Biocompatible Materials↗

PubMedDate not supplied

Development of an artificial extracellular matrix. Solution castable polymers with cell recognizable peptidyl side chain.

This article reports a novel cell-adhesion-promoting polymeric system as an adhesive-protein model. The characteristic features of the system are that polymers have recognition sites and are solution-castable on material surfaces. These co-polymers were prepared by radical co-polymerization of styrene with peptidyl macromer, which include an Arg-Gly-Asp (RGD) sequence, the minimal core peptide recognizable by cell adhesion receptors. Upon casting and subsequent immersion into water, RGD-peptide chains were enriched at the interface with water. Bovine endothelial cells (ECs) adhered to the cast surface, and adhesion was partly directed by RGD-recognition mechanisms. These co-polymers, incorporated with artificial bioactive ligands, may provide an artificial extracellular matrix (ECM) for implantable devices and hybrid organs using a conventional solution-casting technique.

Amino Acid Sequence↗

PubMedDate not supplied

Development of a novel potent peptidyl platelet preserving agent: molecular design and biologic activity.

This paper reports the molecular design of potent peptidyl platelet preserving agents. The principal structural feature of the designed agents has an RGD(Arg-Gly-Asp) sequence in a molecule, which is the adhesive site of adhesive proteins, such as fibrinogen. From conformational analyses and inhibitory effects on adhesion and aggregation of platelets, the logical design criteria aimed at enhanced antiplatelet activities depended upon enforcement of beta-turn structure or spacial rigidity of RGD sequences. The dose-dependent inhibitory effect on platelet aggregation induced by collagen showed that a ten-fold higher activity was found for a linear decapeptide, VVVRGDSVVV (V = Val), and a 100-fold increase for cyclic tetrapeptide, cyclo(RGDG), as compared with RGDS (half inhibition concentration, 0.1 mmol/L). Very potent antiplatelet agents, specially designed for the cardiopulmonary circulation, were successfully developed.

Blood Platelets↗