DsRNA sequencing revealed a previously missed terminal sequence of a +ssRNA virus that infects dinoflagellate Heterocapsa circularisquama.

Heterocapsa circularisquama RNA virus (HcRNAV) is the only dinoflagellate-infecting RNA virus cultured. However, only two strains of HcRNAV have been registered with complete genome sequences (strains 34 and 109 for UA and CY types, respectively). To extend the genomic information of HcRNAV, we performed full-genome sequencing of an unsequenced strain of HcRNAV (strain A8) using the fragmented and primer-ligated double-stranded RNA (dsRNA) sequencing (FLDS) method. The complete genome of HcRNAV A8 with 4457 nucleotides (nt) was successfully determined, and sequence alignment of the major capsid protein gene suggested that A8 was a UA-type strain, consistent with its intraspecific host specificity. The complete sequence was found to be 80 nt longer at the 5' terminus than the registered sequences of HcRNAV strains (34 and 109), suggesting that FLDS is more reliable for determining the terminal sequence than conventional methods (5' Rapid Amplification of cDNA End). Our study contributes to a better understanding of dinoflagellate-infecting viruses with limited sequence data.

Factors associated with drug retention of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: A multicentre REVEAL cohort study.

OBJECTIVES: To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort). METHODS: Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes were collected retrospectively. The patients were stratified into MPZ continuation (n=53) and discontinuation (n=7) groups, and drug retention was statistically compared using the log-rank test. RESULTS: The median age of patients was 54.5 years, with 55% females, and 33% antineutrophil cytoplasmic antibody-positive at disease onset. MPZ exhibited a retention rate of 78.7% after five years. The reasons for discontinuation included treatment of coexisting diseases, inadequate response, and remission. Patient characteristics at disease onset were comparable between the groups. Patients receiving immunosuppressants (IS) before MPZ introduction demonstrated significantly higher retention rates (P = 0.038). During the final observation, the MPZ continuation group had a lower vasculitis damage index score (P = 0.027). CONCLUSIONS: MPZ exhibited a high 5-year retention rate, particularly in patients requiring IS. This study implies that long-term use of MPZ may mitigate irreversible organ damage.

Innovative formulae for the estimation of standard liver volume in the era of widespread imaging analysis software.

BACKGROUND: Various formulae have been used for the estimation of standard liver volume (SLV) in preparation for living donor liver transplantation (LDLT). However, these formulae have the disadvantage of being constructed using parameters that are substantially affected by the patient's condition. Here, we aimed to establish more precise formulae that are less affected by the general condition of the patient. METHODS: We analyzed the liver volumes of LDLT donors and patients with normal livers (total: n = 213) using the SYNAPSE VINCENT imaging analysis system, to develop new formulae. The accuracy of the new formulae were compared with those of existing formulae in a separate validation group of healthy patients (n = 200). The new formulae were also validated using 81 LDLT recipients to assess their utility for graft selection in LDLT. RESULTS: Body surface area (BSA) and skeletal muscle mass index (SMI) independently affected total liver volume (TLV). We produced new formulae for SLV incorporating SMI: SLV = 32.2 × L3-SMI-466.9 for men, with R2 .92, and 25.7 × L3-SMI-55.97 for women, with R2 .79 (alongside a BSA formula with R2 .57), which provided the most accurate predictions of TLV in the validation group. A graft volume (GV)/SLV <.35, calculated using the new formulae, predicted the postoperative prognosis, including the development of small-for-size syndrome, sepsis, or acute rejection, significantly more effectively than GV/SLV using the previous formulae. CONCLUSIONS: The newly developed L3-SMI-based formula is more accurate for the estimation of SLV than previously reported formulae, and may thus help to improve the safety of LDLT.

A sulfur-33 nuclear quadrupole resonance study of 33 S2 -labeled L-cystine.

The sulfur electric-field-gradient tensor for a disulfide bond in 33 S2 -labeled L-cystine has been investigated by 33 S nuclear quadrupole resonance (NQR). 33 S2 -labeled L-cystine is synthesized by introduction of disulfide ions prepared from elemental 33 S-sulfur into an amino acid derivative, the side chain of which is iodinated. In its NQR spectrum, sharp single peaks are observed at between 24.63 and 24.90 MHz in the temperature range from 80 to 298 K. The two-dimensional nutation echo 33 S NQR experiment is carried out at 160 K, and the quadrupole coupling constant, CQ , and the asymmetric parameter, ηQ , are obtained to be 46.9(9) MHz and 0.6(1), respectively. The calculated 33 S electric-field-gradient tensor components with respect to the molecular frame is briefly discussed.

Solution and solid-state 33 S NMR studies of 33 S-labeled taurine.

Sulfur-33(33 S) stable-isotope labeled taurine, 2-aminoethanesulfonic acid, has been synthesized, and a series of solution and solid-state 33 S nuclear magnetic resonance (NMR) experiments at 14.1 and 18.8 T, respectively, have been carried out at room temperature. The single peak of a solution 33 S NMR spectrum in 0.1-mM [33 S]-taurine in D2 O can be observed with the signal-to-noise (S/N) ratio of 9 in 40,000 scans, which paves the way toward in vivo analysis of pharmacokinetics and metabolism of 33 S-labeled taurine. Undistorted magic-angle-spinning (MAS) and static 33 S NMR spectra of polycrystalline [33 S]-taurine are observed with sufficient S/N ratios for analysis, and the magnitudes of 33 S EFG and CS tensors can be obtained.

Progress testing of an objective structured clinical examination during undergraduate clinical clerkship: a mixed-methods pilot study.

BACKGROUND: Progress testing is an assessment method in which an examination reflecting competencies at graduation is regularly administered to students over multiple years, thereby facilitating self-directed learning. However, the significance of the objective structured clinical examination as a progress test in undergraduate education, needs to be determined. This study provides evidence of the role of the objective structured clinical examination for progress testing and optimal scoring methods for assessing students in different academic years. METHODS: We conducted a sequential explanatory mixed-methods pilot study. Participants were assessed using the Item Rating Scale, the year-adjusted Global Rating Scale, and the Training Level Rating Scale. The characteristics of each scale were compared quantitatively. In addition, the influence of the objective structured clinical examination as a progress test on learning attitudes was examined. Qualitative data from a post-examination questionnaire were analyzed, using content analysis to explore influences on self-directed learning. RESULTS: Sixth and fifth year clinical students (n = 235) took the objective structured clinical examination progress test. The total Item Rating Scales were recorded (%) as 59.03 ± 5.27 and 52.64 ± 5.08 (p < 0.01); Training Level Rating Scale was 3.94 ± 0.39 vs 3.22 ± 0.42 (p < 0.01); and the year-adjusted Global Rating Scale was 4.25 ± 0.44 vs 4.32 ± 0.52 (no significant difference), for the sixth and fifth year students, respectively. The correlations across stations and the reliability of each station were satisfactory. Four categories were identified in the qualitative analysis: "motivation to learn during the clinical clerkship was promoted," "dissatisfied with being asked about things they had not experienced," "confusion about being unable to use conventional test-taking strategies," and "insufficient understanding of competencies at graduation." The scores indicated significant differences in performance according to training year. CONCLUSIONS: This study provides evidence that the objective structured clinical examination can be used as a progress testing tool for undergraduate clinical clerkships. Further enhancement of training opportunities and dissemination of performance competency goals in clerkship curricula are required if we intend to promote self-directed learning through progress testing.

Association between Serum Biomarkers and Peripheral Neuropathy in Microscopic Polyangiitis.

This study aimed to elucidate the pathomechanism of peripheral neuropathy (PN) in microscopic polyangiitis (MPA) and to identify biomarkers useful for diagnosis and severity assessment. Patients with MPA (n = 37) and other non-inflammatory neurological diseases (ONDs; n = 12) were enrolled, and the peripheral nerves of all patients were evaluated using nerve conduction studies. We compared the clinical characteristics and 14 serum biomarker profiles among patients with MPA and PN, MPA without PN, and ONDs. Patients with MPA had a higher prevalence of motor neuropathy than patients with ONDs. Among the patients with MPA, those with motor neuropathy had significantly higher total Birmingham Vasculitis Activity Scores and serum levels of C-reactive protein (CRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and interleukin-6 than patients without motor neuropathy. Multivariable analyses adjusted for age, serum CRP level, and diabetes mellitus showed that high serum levels of TIMP-1 were independently related to a diagnosis of motor neuropathy in MPA. Additionally, there were significant negative correlations between the serum levels of TIMP-1 and compound muscle action potential amplitudes. Serum levels of TIMP-1 may be associated with the pathomechanism of motor neuropathy in MPA and could be a useful biomarker for diagnosing and evaluating the severity of motor neuropathy in MPA.

Solid-phase synthesis and bioactivity evaluation of cherimolacyclopeptide E.

Cherimolacylopeptide E (1) is a cyclic hexapeptide isolated from the seeds of Annona cherimola. Peptide 1 reportedly exhibits potent cytotoxicity against KB cells (IC50 0.017 µM). To confirm the structure and bioactivity of 1, we conducted a total synthesis of its proposed structure. The synthesis was accomplished via solid-phase peptide elongation and macrocyclization by employing Fmoc/OAll-protected amino acids on 2-Cl-trityl resin. NMR analysis revealed that synthetic 1 exists in two conformations in pyridine-d5 . As the spectroscopic data of the major conformer of synthetic 1 were consistent with those of natural 1, the structure of cherimolacyclopeptide E was confirmed to be 1. However, our synthetic 1 exhibited low cytotoxicity against KB cells (IC50 > 100 µM). In contrast to previously-reported findings, our synthetic 1 exhibited little antibacterial activity against Escherichia coli.

Bioactive 3D structures of naturally occurring peptides and their application in drug design.

Naturally occurring peptides form unique 3D structures, which are critical for their bioactivities. To gain useful insights into drug design, the relationship between the 3D structure and bioactivity of the peptides has been studied. Solid-state nuclear magnetic resonance (NMR) analysis of the 42-residue amyloid ß-protein (Aß42) suggested the presence of toxic conformers with a turn structure at positions 22 and 23 in the aggregates. Antibodies specific to this turn structure could be utilized for immunotherapy and early diagnosis of Alzheimer's disease. Solution NMR analysis of apratoxin A, a cyclic depsipeptide with potent cytotoxicity, proposed an accurate structural model with an important bend structure, which led to the development of highly active mimetics. X-ray crystal analysis of PF1171F, a cyclic hexapeptide with insecticidal activity, indicated the formation of 4 intramolecular hydrogen bonds, which play an important role in cell membrane permeability of PF1171F.

Design and synthesis of ß-strand-fixed peptides inhibiting aggregation of amyloid ß-protein.

Aggregation of 42-residue amyloid ß-protein (Aß42) can be prevented by ß-sheet breaker peptides (BSBps) homologous to LVFFA residues, which are included in a ß-sheet region of Aß42 aggregates. To enhance the affinity of BSBps to the Aß42 aggregates, we designed and synthesized ß-strand-fixed peptides (BSFps) whose side chains were cross-linked by ring closing metathesis. Conformation analysis verified that the designed peptides could be fixed in ß-strand conformation. Among the synthesized pentapeptides, 1 and 12, whose side chains of 2nd and 4th residues were cross-linked, significantly inhibited the aggregation of Aß42. This suggested that ß-strand-fixation of BSBps could enhance their inhibitory activity against the Aß42 aggregation. However, pentapeptides 1 and 12 had little effect on morphology of Aß42 aggregates (fibrils) and neurotoxicity of Aß42 against SH-SY5Y cells.

Small-for-size syndrome in liver transplantation: Definition, pathophysiology and management.

BACKGROUND: Since the first success in an adult patient, living donor liver transplantation (LDLT) has become an universally used procedure. Small-for-size syndrome (SFSS) is a well-known complication after partial LT, especially in cases of adult-to-adult LDLT. The definition of SFSS slightly varies among transplant physicians. The use of a partial liver graft has risks of SFSS development. Persistent portal vein (PV) hypertension and PV hyper-perfusion after LT were identified as the main factors. Hence, various approaches were explored to modulate PV flow and decrease PV pressure in order to alleviate this syndrome. Herein, the definition, clinical symptoms, pathophysiology, basic research, as well as preventive and treatment strategies for SFSS are reviewed based on an extensive review of the literature and on our own experiences. DATA SOURCES: The articles were collected through PubMed using search terms "liver transplantation", "living donor liver transplantation", "living liver donation", "partial graft", "small-for-size graft", "small-for-size syndrome", "graft volume", "remnant liver", "standard liver volume", "graft to recipient body weight ratio", "sarcopenia", "porcine", "swine", and "rat". English publications published before March 31, 2020 were included in this review. RESULTS: Many transplant surgeons performed PV flow modulation, including portocaval shunt, splenic artery ligation and splenectomy. With these techniques, patient outcome has been improved even when using a "small" graft. Other factors, such as preoperative recipients' nutritional and skeletal muscle status, graft congestion, and donor factors, were also identified as risk factors which all have been addressed using various strategies. CONCLUSIONS: The surgical approach controlling PV flow and pressure could help to prevent SFSS especially in severely ill recipients. In the absence of efficacious medications to resolve SFSS, conservative treatments, including aggressive fluid balance correction for massive ascites, anti-microbiological therapy to prevent or control sepsis and intensive nutritional therapy, are all required if SFSS could not be prevented.

Total Synthesis and Structural Revision of Cyclotetrapeptide Asperterrestide A.

The structural revision of cyclotetrapeptide asperterrestide A has been achieved based on total synthesis and molecular modeling. For these studies, (2 R,3 S)-MePhe(3-OH) and (2 S,3 S)-MePhe(3-OH) suitably protected for peptide synthesis were prepared via a stereoselective reduction of a ketone precursor derived from L- or d-serine, using L-selectride or DIBAL-H. The synthesis of the proposed structure of asperterrestide A (1a) was accomplished by solution-phase synthesis of a linear precursor followed by macrolactamization. The NMR spectra of our synthetic 1a were not identical to those reported for the natural compound. Molecular modeling studies suggested that the correct structure 1b was the one in which the stereochemistry at the α-positions of the Ala and MePhe(3-OH) residues is the opposite to that of the proposed structure. This was confirmed by the total synthesis of 1b and its subsequent structural characterization.

Pretreatment Blood Pressure is a Simple Predictor of Hemorrhagic Infarction after Intravenous Recombinant Tissue Plasminogen Activator (rt-PA) Therapy.

BACKGROUND: Hemorrhagic infarction (HI) is among the most severe complications that can occur following the administration of intravenous recombinant tissue plasminogen activator (rt-PA). In the present study, we aimed to determine the optimal cut-off points of blood pressure (BP) for HI after rt-PA treatment, and to compare our findings with those for other prediction models. METHODS: We analyzed data from 109 consecutive patients with stroke treated at our hospital between 2009 and 2016. HI was confirmed via computed tomography or magnetic resonance imaging. Patients were classified into a symptomatic HI group, an asymptomatic HI group, and a non-HI group. BP was measured on admission and before rt-PA treatment. Glucose Race Age Sex Pressure Stroke Severity (GRASPS) and Totaled Health Risks in Vascular Events (THRIVE) scores were also calculated. Receiver operating characteristic (ROC) analysis was used to determine factors associated with symptomatic and asymptomatic HI. RESULTS: Among the 109 total patients, 25 patients developed symptomatic HI, while 22 patients developed asymptomatic HI. ROC analysis for predicting symptomatic and asymptomatic HI revealed that the area under the curve for pretreatment systolic BP (SBP) was .88 (95% confidence interval[CI]: .83-.94), while those for GRASPS and THRIVE scores were .75 (95% CI: .66-.85) and .69 (95% CI: .59-.79), respectively. We identified an optimal cut-off point of 160 mm Hg (sensitivity: 82.3%; specificity: 76.6%; diagnostic accuracy: 80.0%; positive predictive value: 76.6%; negative predictive value: 82.5%). CONCLUSIONS: Pre-treatment SBP may be a simple predictor of symptomatic and asymptomatic HI in patients with stroke undergoing rt-PA treatment.

RECG maintains plastid and mitochondrial genome stability by suppressing extensive recombination between short dispersed repeats.

Maintenance of plastid and mitochondrial genome stability is crucial for photosynthesis and respiration, respectively. Recently, we have reported that RECA1 maintains mitochondrial genome stability by suppressing gross rearrangements induced by aberrant recombination between short dispersed repeats in the moss Physcomitrella patens. In this study, we studied a newly identified P. patens homolog of bacterial RecG helicase, RECG, some of which is localized in both plastid and mitochondrial nucleoids. RECG partially complements recG deficiency in Escherichia coli cells. A knockout (KO) mutation of RECG caused characteristic phenotypes including growth delay and developmental and mitochondrial defects, which are similar to those of the RECA1 KO mutant. The RECG KO cells showed heterogeneity in these phenotypes. Analyses of RECG KO plants showed that mitochondrial genome was destabilized due to a recombination between 8-79 bp repeats and the pattern of the recombination partly differed from that observed in the RECA1 KO mutants. The mitochondrial DNA (mtDNA) instability was greater in severe phenotypic RECG KO cells than that in mild phenotypic ones. This result suggests that mitochondrial genomic instability is responsible for the defective phenotypes of RECG KO plants. Some of the induced recombination caused efficient genomic rearrangements in RECG KO mitochondria. Such loci were sometimes associated with a decrease in the levels of normal mtDNA and significant decrease in the number of transcripts derived from the loci. In addition, the RECG KO mutation caused remarkable plastid abnormalities and induced recombination between short repeats (12-63 bp) in the plastid DNA. These results suggest that RECG plays a role in the maintenance of both plastid and mitochondrial genome stability by suppressing aberrant recombination between dispersed short repeats; this role is crucial for plastid and mitochondrial functions.

Cyclic Octamer Peptoids: Simplified Isosters of Bioactive Fungal Cyclodepsipeptides.

Cyclic peptoids have recently emerged as an important class of bioactive scaffolds with unique conformational properties and excellent metabolic stabilities. In this paper, we describe the design and synthesis of novel cyclic octamer peptoids as simplified isosters of mycotoxin depsipeptides bassianolide, verticilide A1, PF1022A and PF1022B. We also examine their complexing abilities in the presence of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB) salt and explore their general insecticidal activity. Finally, we discuss the possible relationship between structural features of free and Na⁺-complexed cyclic octamer peptoids and bioactivities in light of conformational isomerism, a crucial factor affecting cyclic peptoids' biomimetic potentials.

Systematic Analysis of the Relationship among 3D Structure, Bioactivity, and Membrane Permeability of PF1171F, a Cyclic Hexapeptide with Paralyzing Effects on Silkworms.

PF1171 hexapeptides, a family of cyclic hexapeptides produced by fungi, exhibit paralyzing effects on the larvae of silkworms via oral administration. To elucidate the structural features of PF1171 hexapeptides that are crucial for bioactivity, the relationship among 3D structure, bioactivity, and membrane permeability of PF1171F (the peptide with the highest bioavailability) was systematically analyzed through the synthesis of 22 analogues. The PF1171F analogues were prepared by the solid-phase synthesis of a linear precursor and subsequent solution-phase macrolactamization. Analysis by NMR spectroscopy and molecular modeling indicated that the major 3D conformations of PF1171F in various solvents resemble its X-ray crystal structure. The analogues with this conformation tend to exhibit potent paralysis against silkworms, indicating the significance of the conformation in the paralysis. The biological activity was dependent on the mode of administration, varying between hemolymph injection and oral administration. Parallel artificial membrane permeability assay (PAMPA) of the analogues revealed a correlation between membrane permeabilities and paralytic activity by hemolymph injection, indicating that the target molecule of PF1171F is present inside the cell membrane.

Potent oxazoline analog of apratoxin C: Synthesis, biological evaluation, and conformational analysis.

In this research, the synthesis, biological evaluation, and conformational analysis of an apratoxin C oxazoline analog (3) have been demonstrated. The preparation of synthetic key intermediate 9 was achieved using an improved strategy that involves commercially available 3-methylglutaric anhydride (12), an enzymatic enantioselective alcoholysis, and a diastereoselective reduction. The Pro-Dtrina (3,7-dihydroxy-2,5,8-trimethylnonanoic acid) moiety 8 was successfully synthesized in a similar manner as our previously reported synthesis of apratoxin C (1). The cyclization precursor 5 was formed after the coupling of Pro-Dtrina 8 with a known tetrapeptide 7 to afford a linear peptide 6, the formation of an oxazoline, and the removal of the protecting groups. Finally, the macrolactamization of 5 with O-(7-aza-1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU)/N,N-diisopropylethylamine (DIEA) furnished an apratoxin C oxazoline analog (3), which exhibited a potent cytotoxicity against HeLa cells (IC50 value of 22 nM) that was comparable with the cytotoxicity of apratoxin C (1) (IC50 value of 4.2 nM). Conformational analyses of 1 and 3 through NMR experiments showed that oxazoline analog 3 formed a tertiary structure that was similar to the apratoxin C (1) structure in CD3 CN, which provided a probable explanation for their comparable cytotoxicities. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 404-414, 2016.

Design, Synthesis, and Biological Evaluation of Beauveriolide Analogues Bearing Photoreactive Amino Acids.

Beauveriolides I and III, which are naturally occurring cyclodepsipeptides, have been reported to bind to sterol O-acyltransferase (SOAT), inhibiting its ability to synthesize cholesteryl esters. To facilitate an analysis of the binding site(s) of these compounds, we designed beauveriolide analogues 1a-d wherein the Leu or D-allo-Ile residue was replaced by photoreactive amino acids possessing methyldiazirine or trifluoromethyldiazirine in the side chains. The methyldiazirine moiety was installed by reaction of methyl ketones with liquid ammonia to provide imine intermediates, followed by treatment with hydroxylamine-O-sulfonic acid to provide the diaziridines. Subsequent oxidation gave methyldiazirines. In contrast, trifluoromethyldiazirine derivatives were prepared from trifluoromethyl ketones via the oxime intermediates, which were transformed into diaziridines. Subsequent oxidation afforded trifluoromethyldiazirines. The synthesized photoreactive amino acids 3a-d were coupled with 3-hydroxy-4-methyloctanoic acid 4 and dipeptide 5, followed by macrolactamization to provide beauveriolide analogues 1a-d. The SOAT inhibitory activities of 1a-d were found to be as potent as those of beauveriolides I and III. Moreover, 1a-d inhibited SOAT1 selectively rather than SOAT2, which was also consistent with the behavior of beauveriolides I and III.

Structure Revision of Similanamide to PF1171C by Total Synthesis.

The total synthesis of the proposed structure of similanamide, a cyclic hexapeptide recently isolated from the marine sponge-associated fungus Aspergillus similanensis KUFA 0013, was achieved by solid-phase synthesis of a linear precursor and solution-phase macrolactamization. The NMR spectra of our synthetic final product were not identical to those of the isolated material and led us to conclude that similanamide is identical to PF1171C, a previously reported diastereomeric hexapeptide.

Site-specific inhibitory mechanism for amyloid ß42 aggregation by catechol-type flavonoids targeting the Lys residues.

The aggregation of the 42-residue amyloid ß-protein (Aß42) is involved in the pathogenesis of Alzheimer disease (AD). Numerous flavonoids exhibit inhibitory activity against Aß42 aggregation, but their mechanism remains unclear in the molecular level. Here we propose the site-specific inhibitory mechanism of (+)-taxifolin, a catechol-type flavonoid, whose 3',4'-dihydroxyl groups of the B-ring plays a critical role. Addition of sodium periodate, an oxidant, strengthened suppression of Aß42 aggregation by (+)-taxifolin, whereas no inhibition was observed under anaerobic conditions, suggesting the inhibition to be associated with the oxidation to form o-quinone. Because formation of the Aß42-taxifolin adduct was suggested by mass spectrometry, Aß42 mutants substituted at Arg(5), Lys(16), and/or Lys(28) with norleucine (Nle) were prepared to identify the residues involved in the conjugate formation. (+)-Taxifolin did not suppress the aggregation of Aß42 mutants at Lys(16) and/or Lys(28) except for the mutant at Arg(5). In addition, the aggregation of Aß42 was inhibited by other catechol-type flavonoids, whereas that of K16Nle-Aß42 was not. In contrast, some non-catechol-type flavonoids suppressed the aggregation of K16Nle-Aß42 as well as Aß42. Furthermore, interaction of (+)-taxifolin with the ß-sheet region in Aß42 was not observed using solid-state NMR unlike curcumin of the non-catechol-type. These results demonstrate that catechol-type flavonoids could specifically suppress Aß42 aggregation by targeting Lys residues. Although the anti-AD activity of flavonoids has been ascribed to their antioxidative activity, the mechanism that the o-quinone reacts with Lys residues of Aß42 might be more intrinsic. The Lys residues could be targets for Alzheimer disease therapy.