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Biomedical subjects

D Yamashiro

Publications and source records attributed to D Yamashiro.

At least 55 records · Page 3Linked to original sources
PubMed1982

Beta-endorphin: replacement of tyrosine in position 27 by tryptophan increases analgesic potency--preparation and properties of the 2-nitrophenylsulfenyl derivative.

An analog of human beta-endorphin with tryptophan in position 27 has been synthetized by the solid-phase method. Bioassay of the analog showed that it had almost 4 times the analgesic potency of the parent hormone but only 68% of the opiate receptor-binding activity. The peptide is the most potent analgesic among the known synthetic analogs of beta-endorphin. The 2-nitrophenylsulfenyl derivative of the analog has been prepared and shown to have a lower analgesic potency and a higher opiate receptor-binding activity than the parent compound.

Amino Acid Sequence↗
PubMed1982

Synthesis and properties of human beta-endorphin-(1-17) and its analogs.

Four analogs of human beta-endorphin (beta h-EP) were synthesized by the solid-phase method: beta h-EP-(1-17) (I), [D-Ala2]beta h-EP-(1-17) (II), [Gln8]-beta h-EP-(1-17) (III) and [D-Ala2, Gln8]-beta h-EP-(1-17) (IV). Measurement in a radio-receptor binding assay with use of tritiated beta h-EP as primary ligand gave relative potencies as follows: Met-enkephalin, 100; I, 33; II, 47; III, 889; IV, 123; beta h-endorphin, 2253.

Amino Acids↗
PubMed1982

beta-Endorphin: synthesis and properties of analogs modified in positions 8 and 31.

Four analogs of human beta-endorphin (beta h-EP) were synthesized by the solid-phase method: [Gln8,31]-beta h-EP(I), [Arg8,Gln31]-beta h-EP(II), [Ala8,Gln31]-beta h-EP (III), and [Val8, Gln31]-beta h-EP(IV). Radioreceptor binding assay with use of tritiated beta h-EP as primary ligand gave relative potencies as follows: beta h-EP, 100; I, 200;II, 150;III, 150;IV, 120. Relative potencies in an analgesic assay were: beta h-EP, 100; I,236;II, 254;III, 116;IV, 121. The side-chain of Glu-8 in beta h-EP can be replaced by a variety of structures without diminishing biological activity.

Amino Acid Sequence↗
PubMed1982

Reduction of methionine sulfoxide in peptide synthesis by use of 2-mercaptopyridine in liquid hydrogen fluoride.

Methionine d-sulfoxide can be reduced to methionine in liquid hydrogen fluoride in the presence of 2-mercaptopyridine. The utility of the reaction in peptide synthesis was demonstrated by preparation of the model peptide H-Leu-Gly-Arg-Leu-Gly-Met-Phe-OH (I) by the solid-phase method. When the peptide resin H-Leu-Gly-Arg(Tos)-Leu-Gly-Met(d-sulfoxide)-Phe-resin is treated in liquid HF in the presence of the standard scavenger anisole, H-Leu-Gly-Arg-Leu-Gly-Met(d-sulfoxide)-Phe-OH (II) is obtained in ca. 66% overall yield with no detectable trace of I. When the same peptide resin is treated in like manner in the added presence of 2-mercaptopyridine, I is obtained in ca. 63% overall yield with no detectable trace of II.

Hydrofluoric Acid↗
PubMed1982

Synthesis and properties of human gamma-lipotropin.

The synthesis of human gamma-lipotropin by the solid-phase method is described. The synthetic product was characterized by Rf in partition chromatography on Sephadex G-50, paper electrophoresis, polyacrylamide gel electrophoresis, thin-layer chromatography, HPLC, end group determination, peptide mapping of a tryptic digest, and amino acid analyses of acid and enzymic digests. The synthetic material is identical to natural human gamma-lipotropin when assayed against natural human beta-lipotropin for lipolytic activity.

Amino Acid Sequence↗
PubMed1982

Synthesis and properties of human beta-endorphin-(1-9) and its analogs.

Four analogs of human beta-endorphin (beta h-EP) were synthesized by the solid-phase method: beta h-EP-(1-9) (I), [D-Ala2]-beta h-EP-(1-9) (II), [Gln8]-beta h-EP-(1-9) (III), and [D-Ala2, Gln8]-beta h-EP-(1-9) (IV). Measurement in a radioreceptor binding assay with use of tritiated beta h-EP as primary ligand gave relative potencies as follows: Met-enkephalin, 100; I, 76; II, 100; III, 200; IV, 200. Two new amino acid derivatives were prepared and used for synthesis of the analogs: N alpha-t-butyloxycarbonyl-O-(cyclopentyl)-tyrosine and N alpha-t-butyloxycarbonyl-gamma-(cyclopentyl)-glutamic acid.

Amino Acid Sequence↗
PubMed1982

beta-Endorphin: synthesis and properties of human beta-endorphin-(1--28) and its analogs.

Three analogs of human beta-endorphin (beta h-EP) were synthesized by the solid-phage method: beta h-EP-(1--28) (I). [Gln8]-beta h-EP-(1--28) (II), and [D-Ala2, Gln8]-beta h-EP-(1--28) (III). Radioreceptor binding assay with use of tritiated beta h-EP as primary ligand gave relative potencies as follows: beta h-EP, 100; I, 85; II, 380; III, 146. Relative potencies in an analgesic assay were: beta h-EP; 100; I, 18; II, 36; III, 13.

Amino Acid Sequence↗
PubMed1982

Beta-Endorphin. Synthesis and properties of double-headed and related analogs.

A double-headed analog of human beta-endorphin (betah-EP), N,N'-bis (beta-endorphinyl)-cystine (II), has been synthesized by the solid-phase method, along with betah-EP-Cys(CH2CONH2)-OH (I) and [Tyr31]-betah-EP (III). Their relative potencies in a radioreceptor-binding assay were: betah-EP, 100; II, 235; I, 170; and III, 204. In the tail-flick test for analgesic activity their relative potencies were: betah-EP, 100; II, 86; I, 93; and III, 116.

Amino Acid Sequence↗
PubMed1981

Human beta-endorphin: synthesis and biological activity of analogs with substitutions in positions 2, 9, 18, 27 and 31.

Four analogs of the opioid peptide human beta-endorphin (Bh-EP) have been synthesized: [D-Lys9, Phe27, Gly31]-beta h-EP, [D-PHe18,Phe27,Gly31]-beta h-EP, [D-Thr2,D-Lys9,Phe27,Gly31]-beta h-EP, and [D-Thr2,D-Phe18,Phe27,Gly31]-beta h-EP. All are practically indistinguishable from beta h-EP in the guinea pig ileum assay. All show diminished analgesic potency in the mouse tail-flick assay.

Amino Acid Sequence↗
PubMed1981

Beta-Endorphin: synthesis and radioreceptor binding activity of Beta h-endorphin-(1-27) and its analogs.

Beta h-Endorphin-(1-27) (I), [Ac-Tyr1]-beta h-endorphin-(1-27) (II), [Gln8]-beta h-endorphin-(1-27) (III), and [Ac-Tyr1, Gln8]-beta h-endorphin-(1-27) (IV) were synthesized by the solid-phase method. The binding potency of I-IV to rat brain membrane preparations was measured by radioreceptor binding assay. The relative potencies were: beta h-endorphin, 100; I, 30; II, 0.04; III, 90; IV, 0.07.

Amino Acid Sequence↗
PubMed1981

beta-Endorphin: isolation, amino acid sequence and synthesis of the hormone from horse pituitary glands.

Beta-endorphin has been isolated from equine pituitaries. Its amino acid sequence is identical to that of ovine, bovine and camel beta-endorphins except for substitution of the threonine residue at position 6 by serine. The equine beta-endorphin has also been synthesized by the solid-phase method. In comparison with the human hormone, equine beta-endorphin was shown to possess 3 times the receptor-binding activity in rat membrane preparations and 1.6 times the analgesic potency in the mouse tail-flick assay.

Amino Acid Sequence↗
PubMed1981

Use of thiol acids in peptide segment coupling in non-aqueous solvents.

Methods for preparing protected peptide thiol acids by solution and solid-phase procedures have been developed. The coupling of boc-Gly-Ala-SH to polymer-bound Leu was effected with dicyclohexylcarbodiimide (DCC), 2,4-dinitrofluorobenzene (FDNB), N-bromosuccinimide (NBS), and heat. In each case, the resulting H-Gly-Ala-leu-OH was analyzed for the content of H-Gly-D-Ala-Leu-OH (Izumiya test). The sensitivity of the test (0.1% epimer) was increased to 0.003% by developing a double chromatographic procedure involving partition chromatography prior to ion-exchange chromatography. The amounts of DL epimer found in the H-Gly-Ala-Leu-OH for the various tests were (solvent and temperature in parentheses): DCC (CH2Cl2, 0 degrees), 0.012%; DCC (DMF, 24 degrees),0.04%; FDNB (DMF, 24 degrees), 0.53%; NBS (DMF, 24 degrees), 0.46%, heat (DMF, 60 degrees), 0.86%. Under the same conditions conventional couplings of Boc-Gly-Ala-OH gave: DCC (DMF, 24 degrees), 16.5%; DCC/1-hydroxybenzotriazole (DMF, 24 degrees), 0.13%. In a competitive coupling of equimolar amounts of Boc-Gly-Ala-SH and Boc-Gly-Ala-OH with DCC in DMF the level of DL epimer was 0.21%, indicating that the thiol acid can be selectively coupled in the presence of carboxyl groups. In a variation of the test Boc-Gly-Leu-SH coupled with DCC (CH2Cl2, 0 degrees) to resin bound Ala with an epimer level of 0.05%.

Bromosuccinimide↗
PubMed1981

Synthesis of a corticotropin analog that retains full biological activity after iodination.

In order to circumvent the drastic decrease in biological activity that accompanies iodination of corticotropin, we have synthesized an analog of the human hormone containing phenylalanine in place of tyrosine in position 2 and norleucine in place of methionine in position 4 to give [Phe2,Nle4]ACTH-(1-38). This analog, referred to as Phe2,Nle4-ACTH-(1-38), was purified by ion exchange chromatography and partition chromatography. Phe2,Nle4-ACTH-(1-38) was found to be indistinguishable from synthetic human ACTH in its ability to stimulate corticosterone production in isolated rat adrenocortical cells. Iodination of Phe2,Nle4-ACTH-(1-38) resulted in the formation of monoiodo-Tyr23,Phe2,Nle4-ACTH-(1-38) and diiodo-Tyr23,Phe2,Nle4-ACTH-(1-38), which were completely separated from each other and unmodified Phe2,Nle4-ACTH-(1-38) by reverse phase high performance liquid chromatography. Monoiodo-Tyr23,Phe4,Nle4-ACTH-(1-38) was also found to be as potent as ACTH in stimulating steroidogenesis. These results show that Phe2,Nle4-ACTH-(1-38) can be used for the preparation of the radioligand with full biological activity for studying physiologically relevant corticotropin receptors and for use in RIA.

Adrenal Cortex↗