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K Akaji

Publications and source records attributed to K Akaji.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Idiopathic intracranial hypotension associated with decreased blood concentration of vitamin A].

We report a case of idiopathic intracranial hypotension, a clinically rare syndrome. A 28-year-old woman was admitted with orthostatic headaches associated with nausea secondary to intracranial hypotension. Lumbar puncture yielded an opening pressure of 4 cmH2O in the lateral recumbent position, and the spinal fluid protein concentration was 56 mg/dl. There was no history of lumbar puncture or clear history of head trauma before the onset of symptoms. Spinal and cranial MRI showed no evidence of CSF leakage, and there was diffuse meningeal enhancement following gadolinium infusion. Cranial MRI showed no evidence of brain displacement due to low CSF pressure, such as tonsillar herniation. Radioisotope cisternography (RIC) showed rapid accumulation of isotope within the bladder and early disappearance of radioactivity from the head. About 2 months later the headaches resolved spontaneously, and repeated lumbar puncture yielded opening pressure elevation to 10.5 cmH2O with a decrease in protein concentration to 28 mg/dl. The abnormal MRI and RIC findings had become normal. On the other hand, the patient had a low blood concentration of vitamin A, which is thought to play some role in the production of CSF. The results of RIC suggested that the patient may have become symptomatic because of undetectable CSF leakage or hyperabsorption, but diminished production of CSF due to lower blood vitamin A concentrations may also have been a factor predisposing to this syndrome.

Adult↗
PubMed1994

Racemization-free synthesis of C-terminal cysteine-peptide using 2-chlorotrityl resin.

We investigated the effects of bases, resins, and S-protecting groups on the extent of racemization at the C-terminal cysteine during Fmoc-based(Fmoc=fluoren-9-yl-methoxy-carbonyl) solid phase peptide synthesis. The use of 2-chlorotrityl resin was most effective in suppressing the racemization caused by the base treatment for Fmoc-cleavage. Somatostatin was successfully synthesized with practically no racemization using 2-chlorotrityl resin by Fmoc-chemistry.

Chromatography, High Pressure Liquid↗
PubMed1993

Synthesis of rat brain natriuretic peptide 45 using tetrafluoroboric acid deprotection and silyl chloride disulfide formation.

A newly isolated rat brain natriuretic peptide 45 (rBNP45) was synthesized using the 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase method. Tetrafluoroboric acid (HBF4) deprotection was successfully applied for this synthesis, while the conventional trifluoroacetic acid (TFA)-thioanisole method gave unsatisfactory results. The disulfide bond of rBNP45 was constructed by using the silyl chloride method within 10 min, which was extremely advantageous to avoid the formation of Met(O)-rBNP45. The chick rectum relaxant activity of the synthetic rBNP45 was three times as potent as that of alpha-rat atrial natriuretic peptide (alpha-rANP).

Amino Acid Sequence↗
PubMed1992

Synthesis and biological evaluation of a 13N-labeled opioid peptide.

The 13N-labeled opioid tetrapeptide, Tyr-D-Met(O)-Phe-Gly-[13N]NH2 (SD-62), was synthesized by amidation of its activated p-nitrophenol ester with [13N]ammonia (total synthesis time: 25 min, radiochemical yield: 48%). When injected intravenously into mice, [13N]SD-62 was taken up by the brain and this uptake was blocked by naloxone. In addition, the time course of changes in brain radioactivity paralleled that of the analgesic activity of this compound, suggesting that SD-62 underwent binding to brain opioid receptors. Thus, [13N]SD-62 appears to hold some promise for use as a radiopharmaceutical for in vivo studies of opioid peptide behavior, using positron emission tomography.

Amino Acid Sequence↗
PubMed1992

Kynostatin (KNI)-227 and -272, highly potent anti-HIV agents: conformationally constrained tripeptide inhibitors of HIV protease containing allophenylnorstatine.

Selective and potent HIV protease inhibitors containing allophenylnorstatine [Apns; (2S, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid] as a transition-state mimic were designed and synthesized. Among them, conformationally constrained tripeptide derivatives, kynostatin (KNI)-227 and -272 (Fig. 1), exhibited highly potent antiviral activities against a wide spectrum of HIV isolates. Ready availability due to the simple synthetic procedure and the excellent antiviral properties indicate that KNI-227 and KNI-272 are promising candidates as selective anti-AIDS drugs.

Antiviral Agents↗
PubMed1991

A synthetic method suitable for the rapid preparation of 13N-labeled dermorphin analogue, H-Tyr-D-Met(O)-Phe-Gly-NH2 (SD-62).

A synthetic method suitable for the preparation of 13N-labeled dermorphin analogue, H-Tyr-D-Met(O)-Phe-Gly-NH2 (SD-62), was established; i.e., SD-62 was synthesized by a 5 min treatment of the active ester precursor with ammonia. When the 13N-labeled SD-62, prepared by this method with [13N]ammonia, was administered into mice, the time profile of the radioactivity accumulation in the brain paralleled well that of the analgesic activity.

Analgesics, Opioid↗
PubMed1991

KNI-102, a novel tripeptide HIV protease inhibitor containing allophenylnorstatine as a transition-state mimic.

HIV-1 protease inhibitors containing allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid]-Pro (syn diastereomer) as a transition-state mimic were established to be potent and highly selective. Z-Asn-Apns-Pro-NHBut (KNI-102) is the only tripeptide exhibiting substantial anti-HIV activity and may be of minimum size for potent, selective inhibition of HIV protease. Ready availability due to its simple chemical structure and stability should make it valuable for studies of the development of metabolically stable anti-AIDS drugs.

Amino Acid Sequence↗
PubMed1991

New hydroxyl protecting groups of a safety-catch type removable by reductive acidolysis.

New hydroxyl protecting groups of a safety-catch type, i.e., 4-methylsulfinylbenzyl-oxycarbonyl (Msz) group for Tyr and 4-methylsulfinylbenzyl (Msob) ether for Thr, have been developed. O-Msz and O-Msob groups are stable under both acidic and basic conditions and can be removed by a one-pot reaction involving reductive acidolysis using tetrachlorosilane-trifluoroacetic acid (TFA)-scavengers. Using these new protecting groups, a 17 residue-peptide, gamma-endorphin, was successfully synthesized by the efficient solid phase method.

Amino Acid Sequence↗
PubMed1990

Interleukin-1 beta inhibits long-term potentiation in the CA3 region of mouse hippocampal slices.

The effect of recombinant human interleukin 1-beta (IL-1 beta) on long-term potentiation (LTP) in the mossy fiber-CA3 pathway of mouse hippocampal slice preparations was investigated. IL-1 beta significantly inhibited LTP in concentrations as low as 2.9 pM (50 pg/ml). This effect of IL-1 beta was blocked by concurrent application of 100 nM Lys-D-Pro-Thr, a tripeptide analogue of IL-1 beta. This is the first evidence that IL-1 beta can regulate LTP of synaptic transmission in the hippocampus.

Animals↗
PubMed1990

Solution-phase synthesis of alpha-rat atrial natriuretic peptide (alpha-rANP).

alpha-Rat atrial natriuretic peptide (alpha-rANP) was synthesized by assembling five peptide fragments in solution, followed by HF-dimethylselenide-m-cresol deprotection and subsequent air-oxidation. Synthetic alpha-rANP exhibited more potent diuretic and natriuretic activity in rats than synthetic alpha-hANP.

Amino Acid Sequence↗
PubMed1990

Solution-phase synthesis of porcine brain natriuretic peptide (pBNP) using S-trimethylacetamidomethylcysteine.

The hexadodecapeptide corresponding to the entire amino acid sequence of porcine brain natriuretic peptide (pBNP) was synthesized by assembling four segments in solution, followed by HF deprotection and subsequent oxidation to establish an intramolecular disulfide bridge. The synthesis using the newly developed S-trimethylacetamidomethylcysteine [Cys(Tacm)] derivative gave a better yield than that using the S-2,4,6-trimethylbenzylcysteine [Cys(Tmb)] derivative. The chick rectum relaxant activity of the synthetic pBNP was 2.9 times more potent than that of alpha-rat atrial natriuretic peptide (alpha-rANP).

Amino Acid Sequence↗
PubMed1990

Deprotection of the S-trimethylacetamidomethyl (Tacm) group using silver tetrafluoroborate: application to the synthesis of porcine brain natriuretic peptide-32 (pBNP-32).

Silver tetrafluoroborate (AgBF4) in trifluoroacetic acid (TFA) has been found to cleave the S-trimethyl-acetamidomethyl (Tacm) group or the S-acetamidomethyl (Acm) group without affecting other functional groups in a peptide chain. A newly isolated porcine brain natriuretic peptide-32 (pBNP-32) was synthesized by the combined use of the S-Tacm group and AgBF4 deprotection. The synthetic pBNP-32 was obtained in better yield by the AgBF4 procedure than by the standard I2 procedure. The synthetic pBNP-32 has the highest chick rectum relaxant activity among the known members of the atrial natriuretic peptide-brain natriuretic peptide (ANP-BNP) families. Somatostatin was also synthesized by the Fmoc-based solid-phase method using S-Tacm and AgBF4. In this synthesis, the recently developed reagent tetrafluoroboric acid (HBF4) was applied to cleave the peptide from the resin.

Acetamides↗
PubMed1990

Synthesis of porcine brain natriuretic peptide-32 using silver tetrafluoroborate as a new deprotecting reagent of the S-trimethylacetamidomethyl group.

Silver tetrafluoroborate (AgBF4) in trifluoroacetic acid (TFA) has been found to cleave the S-trimethylacetamidomethyl (Tacm) group or the S-acetamidomethyl (Acm) group without affecting other functional groups in the peptide chain. Newly isolated porcine brain natriuretic peptide-32 (pBNP-32) was synthesized using AgBF4 and Cys(Tacm) derivatives. The synthetic pBNP-32 had the highest chick rectum relaxant activity among the ANP-BNP families.

Amino Acid Sequence↗
PubMed1990

Solution-phase synthesis of alpha-human atrial natriuretic peptide (alpha-hANP).

Alpha-human atrial natriuretic peptide (alpha-hANP) was synthesized by assembling six peptide fragments in solution followed by deprotection with HF and subsequent air-oxidation. The trimethylbenzyl group was employed as an S-protecting group of cysteine. The HF-dimethylselenide-m-cresol system was employed as a final deprotecting reagent and, at the same time, as a reducing reagent of Met(O). Synthetic alpha-hANP elicited potent diuretic and natriuretic activity in rats.

Amino Acid Sequence↗
PubMed1989

Studies on peptides. CLXVII. Solid-phase syntheses and immunological properties of fragment peptides related to human malaria circumsporozoite protein.

A glycine-linked tetramer of Asn-Ala-Asn-Pro, a tandem repeated sequence of malaria circumsporozoite (CS) protein, was synthesized by the Boc-based solid phase method, followed by deprotection with 1 M trimethylsilyl trifluoromethanesulfonate-thioanisole in trifluoroacetic acid. In addition, three tetramer-related peptides were similarly synthesized, i.e., a 34-residue peptide [linked with TH, a proposed T-cell epitope of CS, at the C-terminus of the tetramer], a 46-residue peptide and a 59-residue peptide [linked with HA or HA', two proposed T-cell epitopes of influenza hemagglutinin protein, at the N-terminus of the above 34-residue peptide]. Their immunological properties were examined by enzyme-linked immunosorbent assay, for which three different congenic strains of mouse were used to raise the specific antibodies. Despite conjugation of T-cell epitopes to the tetramer, the mice of low-responder strains to the tetramer failed to produce any antibody specific to the tetramer. However, with the aid of recombinant interleukin 2 as an adjuvant, the low-responder mice produced antibody with relatively high titers.

Antigens, Surface↗
PubMed1989

Tetrafluoroboric acid, a useful deprotecting reagent in peptide synthesis.

We have found that tetrafluoroboric acid (HBF4) in trifluoroacetic acid (TFA) in the presence of thioanisole cleaves various protecting groups currently used in peptide synthesis. HBF4 in TFA cleaves an amino acid amide from 4-methylbenzhydrylamine resin more effectively than trifluoromethanesulfonic acid in TFA. Lamprey gonadotropin-releasing hormone (a 10-residue peptide amide) was synthesized using 1 M HBF4-thioanisole in TFA by both solution-phase and solid-phase methods.

Amino Acid Sequence↗