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K Akaji

Publications and source records attributed to K Akaji.

At least 73 records · Page 4Linked to original sources
PubMed1985

Studies on peptides. CXXVIII. Application of new heterobifunctional crosslinking reagents for the preparation of neurokinin (A and B)-BSA (bovine serum albumin) conjugates.

A decapeptide corresponding to the entire amino acid sequence of neurokinin A, a porcine spinal cord peptide, was synthesized in a conventional manner using protecting groups removable by 1 M TFMSA-thioanisole in TFA. The HS-CH2CH2CO group was introduced onto the synthetic neurokinin A by reaction of 3-(S-acetyl-thiopropionyl)-thiazolidine-2-thione, followed by deacetylation with hydroxylamine. 2,4-Dinitrophenyl-p-(beta-nitrovinyl)-benzoate trapped the above HS-CH2CH2CO-neurokinin A derivative in acidic media, then BSA in basic media in nearly quantitative yield. A similar decapeptide, neurokinin B, was also synthesized and conjugated onto BSA using an alternative SH-introducing reagent, 3-(S-p-methoxybenzyl-thiopropionyl)-thiazolidine-2-thione, and the above heterobifunctional conjugating reagent.

Amino Acid Sequence↗
PubMed1982

Studies on peptides. CXI. Synthesis of chicken gastrin-releasing peptide.

The heptacosapeptide amide corresponding to the entire amino acid sequence of chicken gastrin-releasing peptide (cGRP) was synthesized similarly to the synthesis of porcine GRP by assembling six peptide fragments followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole in TFA. A new carboxyl-activating reagent, thiazolidine-2-thione, was preferentially adopted for preparation of necessary fragments. The synthetic cGRP, purified by ion-exchange chromatography, followed by partition chromatography, was active as the synthetic porcine GRP, when plasma immunoreactive gastrin level was examined in rats. No obvious difference was observed when synthetic and natural cGRP preparations were compared by HPLC, immunochemical property and biological activity in dogs.

Amino Acid Sequence↗
PubMed1981

Studies on peptides. CII. Synthesis of a heptacosapeptide amide corresponding to the entire amino acid sequence of gastrin-releasing peptide.

The heptacosapeptide amide corresponding to the entire amino acid sequence of gastrin-releasing peptide (GRP) was synthesized by assembling seven peptide fragments followed by deprotection with a new reagent system, IM trifluoromethanesulfonic acid-thioanisole in TFA. The deprotected peptide was purified by ion-exchange chromatography on CM-cellulose followed by partition chromatography on Sephadex G-25. The latter was found to remove effectively the Met (O) derivative of GRP. The highly purified synthetic GRP was active as synthetic bombesin on the molar basis. A new carboxyl-activating reagent, thiazoline-2-thione, was employed for preparation of the necessary fragments.

Amino Acid Sequence↗
PubMed1979

Studies on peptides. LXXXI. Application of a new arginine derivative, NG-mesitylene-2-sulfonylarginine, to the synthesis of substance P and neurotensin.

A new devised arginine derivative, NG-mesitylene-2-sulfonylarginine, Arg(Mts), was employed for the synthesis of hypothalamic substance P and neurotensin. The former was obtained in 74% yield by treatment of the protected undecapeptide amide, Z - Arg(Mts) - Pro - Lys(Z) - Pro - Gln - Gln - Phe - Phe - Gly - Leu - Met(O)-NH2, with methanesulfonic acid in the presence of anisole followed by reduction of the sulfoxide with 2-mercaptoethanol. The latter was obtained in 54% yield by the similar treatment of the protected tridecapeptide ester, Z - Pyr - Leu - Tyr - Glu(OBzl) - Asn - Lys(Z) - Pro - Arg(Mts) - Arg(Mts) - Pro - Tyr - Ile - Leu - OBzl, with methanesulfonic acid. As scavenger, a mixture of anisole-thioanisole-o-cresol (1:1:1, by vol.) was employed to suppress the side reaction, O-mesitylene-2-sulfonation of the Tyr residue.

Amino Acid Sequence↗
PubMedDate not supplied

Conventional and high-yield synthesis of DTPA-conjugated peptides: application of a monoreactive DTPA to DTPA-D-Phe1-octreotide synthesis.

Successful imaging of somatostatin receptor-positive tumors with 111In-DTPA-D-Phe1-octreotide has stimulated development of peptide radiopharmaceuticals using DTPA as the chelating agent. However, use of cyclic DTPA dianhydride (cDTPA) resulted in low synthetic yields of DTPA-peptide by either solution or solid-phase syntheses. This paper reports a novel high-yield synthetic procedure for DTPA-D-Phe1-octreotide that is applicable to other peptides of interest using a monoreactive DTPA derivative. A monoreactive DTPA that possesses one free terminal carboxylic acid along with four carboxylates protected with tert-butyl ester (mDTPA) was synthesized. Fmoc-Thr(tBu)-ol, prepared from Fmoc-Thr(tBu)-OH, was loaded onto 2-chlorotrityl chloride resin. After construction of the peptide chains by Fmoc chemistry, mDTPA was coupled to the alpha amine group of the peptide on the resin in the presence of 1,3-diisopropylcarbodiimide and 1-hydroxybenzotriazole. Treatment of the mDTPA-peptide-resin with trifluoroacetic acid-thioanisole removed the protecting groups and liberated [Cys(Acm)2,7]-octreotide-D-Phe1-DTPA from the resin. Iodine oxidation of the DTPA-peptide, followed by the reversed-phase HPLC purification, produced DTPA-D-Phe1-octreotide in overall 31.8% yield based on the starting Fmoc-Thr(tBu)-ol-resin. The final product gave a single peak on analytical HPLC, and amino acid analysis and mass spectrometry confirmed the integrity of the product. 111In radiolabeling of the product provided 111In-DTPA-D-Phe1-octreotide with > 95% radiochemical yield, as confirmed by analytical reversed-phase HPLC, TLC, and CAE. These finding indicated that use of mDTPA during solid-phase peptide synthesis greatly increased the synthetic yield of DTPA-D-Phe1-octreotide, due to the absence of nonselective reactions that are unavoidable when cDTPA is used. These results also suggested that mDTPA would be a versatile reagent to introduce DTPA with high yield into peptides of interest.

Octreotide↗
PubMedDate not supplied

Renal metabolism of 111In-DTPA-D-Phe1-octreotide in vivo.

The persistent localization of radioactivity in the kidney after administration of 111In-DTPA-D-Phe1-octreotide impairs the diagnostic accuracy of this radiopharmaceutical. To better understand the mechanisms responsible for the renal radioactivity levels of 111In-DTPA-D-Phe1-octreotide, the renal metabolism of this compound was compared with 111In-DTPA-L-Phe1-octreotide, where the N-terminal D-phenylalanine was replaced with L-phenylalanine to facilitate metabolism. DTPA-D-Phe1-octreotide and DTPA-L-Phe1-octreotide were synthesized by solid-phase methods. Both 111In-DTPA-conjugated octreotide analogues were prepared with radiochemical yields of over 96%, and both remained stable after a 3 h incubation in murine serum at 37 degreesC. When injected into mice, the two 111In-DTPA-conjugated octreotide analogues showed similar radioactivity elimination rates from the blood and accumulation in the kidney with about 60% injected radioactivity being excreted in the urine by 24 h postinjection. Over 85% of the radioactivity in the urine existed as intact peptides for both analogues. Despite the similar renal radioactivity levels, significant differences were observed in the radiolabeled species remaining in the kidney between the two; while 111In-DTPA-L-Phe1-octreotide was rapidly metabolized to the final radiometabolite, 111In-DTPA-L-Phe, the metabolic rate of 111In-DTPA-D-Phe1-octreotide was so slow that various intermediate radiolabeled species were observed. However, both 111In-DTPA-D-Phe and 111In-DTPA-L-Phe remained in the lysosomal compartment of the renal cells as the final radiometabolites for long periods. These findings indicated that although the metabolic stability of 111In-DTPA-D-Phe1-octreotide in the renal cells may be partially involved, the slow elimination rate of the radiometabolite derived from 111In-DTPA-D-Phe1-octreotide from the lysosomal compartment of renal cells would be predominantly attributable to the persistent renal radioactivity levels of 111In-DTPA-D-Phe1-octreotide.

Animals↗