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R Matsueda

Publications and source records attributed to R Matsueda.

24 records · Page 2Linked to original sources
PubMedDate not supplied

Highly potent and specific inhibitors of human renin.

Small peptide analogues representing the C-terminal portion of angiotensin I sequence were designed as inhibitors of human renin. Among synthesized compounds, benzyloxycarbonyl (-"Z")-(1-naphthyl)Ala-His-leucinal (ES-188), Z-(1-naphthyl)Ala-His-statine ethyl ester (ES-226), and Z-(1-naphthyl)Ala-His-statine 2-methylbutylamide (ES-254) markedly inhibited human and primate renins (inhibitory concentration, 50% [IC50], near 10(-7) M). These peptide analogues inhibited rabbit renin with one or two orders of magnitude less potency. They were very weak inhibitors of renins from pig, goat, dog, and rat. ES-188 had no discernible effect on cathepsin D, pepsin, or human angiotensin-converting enzyme at the concentration of 10(-4)M. ES-226 had little effect on the three enzymes at the concentration of 10(-5)M; however, ES-254 had a considerable inhibitory effect on cathepsin D (IC50 of 1.4 X 10(-5)M), pepsin (IC50 of 4.2 X 10(-5)M), and human angiotensin-converting enzyme (IC50 of 7.1 X 10(-6)M). Our results indicate that 1-naphthylalanine-containing tripeptide analogues are highly potent human renin inhibitors.

Angiotensin I↗
PubMedDate not supplied

Compatibility of the S-(3-nitro-2-pyridinesulfenyl) protecting group with DCC/HOBt coupling chemistry.

Two recent reports on the partial lability of the 3-nitro-2-pyridinesulfenyl (Npys) thiol protecting group towards 1-hydroxy-benzotriazole (HOBt) have prompted a rechecking of the chemical behavior of this group. Using both soluble and polymer-bound forms of Cys(Npys) as test materials, the complete stability of this protection against HOBt has now been definitively established, and its compatibility with Boc-benzyl-based solid-phase synthesis strategies has been clearly confirmed by stability assays against a wide range of reagents, as well as by the successful synthesis of several Cys(Npys)-containing peptides.

Amino Acid Sequence↗
PubMedDate not supplied

Irreversible blockade of the kappa-receptor by a newly synthesized dynorphin derivative containing a 3-nitro-2-pyridinesulfenyl group.

The interactions of the dynorphin derivative containing a 3-nitro-2-pyridinesulfenyl group (dynorphin derivative) with kappa-receptors were studied. The dynorphin derivative inhibited, in a concentration-dependent manner, the twitch response to electrical stimulation of the longitudinal muscle of the guinea-pig ileum which contains both mu- and kappa-receptors. It also inhibited the twitch response to electrical stimulation of the rabbit vas deferens, reported to contain only kappa-receptors; its pD2 value was 11.57 +/- 0.09, suggesting that the agonistic activity of the dynorphin derivative is mainly mediated through kappa-receptors. The KD and Bmax values of [3H]U-69593 were calculated from a Scatchard plot of the specific binding. After a 30 min treatment with 10(-5) M of this dynorphin derivative, the KD value did not alter but the Bmax value decreased. However, this decrease recovered after treatment with 2 x 10(-3) M of dithiothreitol. These results suggest that the dynorphin derivative binds to kappa-receptors through the disulfide bound. The dissociation constant of nalorphine-7,8-oxide (nalorphine-epoxide) was determined according to the method of Furchgott, by irreversibly binding a fraction of the kappa-receptors with the dynorphin derivative. The negative logarithms of the dissociation constants (pKA values) for nalorphine-epoxide did not differ in the guinea-pig ileum and rabbit vas deferens, suggesting that the kappa-receptors in the two preparations are identical. However, the pD2 value and efficacy for nalorphine-epoxide in the guinea-pig ileum were significantly greater than those in the rabbit vas deferens. These results indicate that the kappa-receptor reserve in the longitudinal muscle of the guinea-pig ileum is greater than in the rabbit vas deferens. It is thought that the dynorphin derivative, containing a 3-nitro-2-pyridinesulfenyl group, is useful to clarify the kappa-receptor mechanisms.

Amino Acid Sequence↗
PubMedDate not supplied

Design and synthesis of a kininogen-based selective inhibitor of thrombin-induced platelet aggregation.

Thrombin-induced platelet aggregation has been suggested to play an important role in reocclusion following thrombolytic therapy or angioplasty for treatment of myocardial infarction. We previously demonstrated that thrombin-induced platelet aggregation is indirectly mediated by intracellularly activated calpain expressed on the platelet surface through the cleavage of aggregin, a putative ADP-receptor, and that high molecular weight kininogen (HK), a naturally occurring thiol protease inhibitor, modulates thrombin-induced platelet aggregation. Considering the substrate specificity of calpain and the conserved sequence in HK, we studied selective inhibitors of thrombin-induced platelet aggregation by the affinity labeling approach with an S-3-nitro-2-pyridinesulfenyl (Npys) group. H-Phe-Gln-Val-Val-Cys (Npys)-Gly-NH2, which combines chemical and structural features of calpain substrate specificity and the conserved sequence in HK, selectively inhibited thrombin-induced platelet aggregation. It did not inhibit the aggregatory effects of other platelet agonists, and did not inhibit amidolytic activity of thrombin and thrombin-induced platelet shape change. The design and synthesis of such inhibitors could lead to the development of a new class of inhibitors that selectively block thrombin-induced platelet aggregation.

Amino Acid Sequence↗