In the course of our screening program for new inhibitors of dipeptidyl peptidase III (EC 3.4.14.4), we discovered fluostatins A and B (1 and 2, Fig. 1) from the culture broth of Streptomyces sp. TA-3391. The taxonomy of the producing strain, fermentation, isolation, physico-chemical properties and biological properties have been described in the preceding paper1). Here we report on the structure determination of 1 and 2 on the basis of spectroscopic studies, chemical studies and X-ray crystallographic analysis. The physico-chemical properties of 1 and 2 were described in the previous paper1). The molecular formulae of 1 (C18H10O5) and 2 (C18H14O6) were determined by interpretation of the HRFAB-MS, NMR spectral analyses and elemental analyses. The 1H and 13C NMR spectra of 2 showed the presence of twelve protons and eighteen carbons. The DEPT experiment revealed that these carbons consisted of two carbonyls, twelve other sp2 and four sp3 carbons. The carbons bearing protons were assigned by a Heteronuclear Single Quantum Coherence (HSQC) experiment. These data are summarized in Table 1. Two partial structures of 2 were established on the basis of 1H-1H coupling constants in the 1H NMR spectrum and Heteronuclear Multiple Bond Correlation (HMBC) experiment (Fig. 2-b). A 4-bond coupling

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Aminopeptidase N [AP-N, EC 3.4.ll.2] is a Zn2+dependent ectoenzyme that is anchored in the plasma membranevia a hydrophobic domain adjacent to a small cytoplasmic region at the NH2terminus1'2). This enzyme is widely expressed by the brush border of the small intestine, synaptic cells of the central nervous system, and hematopoietic cells of myeloid lineage3). It has been postulated that AP-N performs multiple functions to regulate the action of hormonesand neurotransmitters by inactivating such peptides at the cell surface4'5).

Previously, we reported protease changes in cerebral tissues, as well as in serum, of patients with Alzheimer-type dementia. In the present study, we investigated enzymatic activities in their cerebrospinal fluid. In the Alzheimer patients the activities of dipeptidyl peptidase III (DPP-III), DPP-IV, and cathepsin B were significantly increased when compared with those of the control subjects. In vascular dementia patients the activities of Leu-AP and cathepsin B were increased but the activity of DPP-III was decreased. These results, as well as those of a multivariate study on these enzymatic changes, suggest the independency of the cerebral changes in the Alzheimer patients from those in vascular dementia. The results may also be of use for clinical diagnoses of these pathologic states.

Previously we reported that there is a kallikrein deficiency in the cerebral tissue of patients with Alzheimer-type dementia. The present study was performed to investigate protease changes in the serum of these patients. The results showed that the kallikrein activity was normal, but that the activities of plasmin and urokinase were significantly low. The present findings indicate a derangement in the clotting and fibrinolytic systems in Alzheimer patients.